PATENT ABSTRACT
Method and device for the in vitro analysis of mRNA of genes involved in hematological neoplasias. The device, composed of probes which specifically hybridize with genes involved in hematological neoplasias, designed so that its behaviour in the hybridization is similar, permits the evaluation of the mRNA level in biological samples taken from subjects suspected to be suffering from hematological neoplasia and facilitating the comparison between the different samples and their grouping by similarity in the gene expression patterns, especially when the probes are disposed in the form of microarray. The application of the method of the invention to obtain and process data of gene expression differences from the device of the invention permits the identification of genes significant for distinguishing samples associated to hematological neoplasias, facilitates the diagnosis of neoplasias as CLL and permits making a prognosis of the evolution thereof.

PATENT DESCRIPTION
FIELD OF THE INVENTION 
       [0001]    The invention relates to the technical-industrial sector of the extracorporeal in vitro diagnosis of biological samples, by genetic engineering techniques, applied to the diagnosis of specific types of neoplasias from their gene expression patterns and/or to the prognosis of their evolution. More specifically, the invention relates to the identification of neoplasias originating from hematopoietic cells from the evaluation of the levels of messenger RNA of significant genes in biological samples such as peripheral blood samples, preferably by the use of microarrays. With this it is possible to identify samples corresponding to patients suffering from CLL, permitting the diagnosis thereof and, furthermore, it is possible to classify samples from patients suffering from CLL in samples which belong to patients wherein the CLL is going to remain stable or wherein it is going to progress, enabling the prognosis of the future evolution of these patients. 
       BACKGROUND OF THE INVENTION 
       [0002]    Each day, the human body produces billions of new white and red cells and platelets which replace the hematopoietic cells which are lost as a consequence of a normal process of renewal, disease or trauma. The organized production process of hematopoietic cells and homeostasis is known with the name of hematopoiesis (Weissman I L et al., 2000; Leung A Y H et al., 2005. 
         [0003]    In man, hematopoiesis is confined to the bone marrow (B.M.) of the greater part of the bones, and gradually, with age, this is replaced by fat, which in the adult, 70% of the bone marrow is located in the pelvis, vertebra and sternum (Bernard et al., 1976). 
         [0004]    All the mature blood cells are generated from a relatively low number of hematopoietic cells known hematopoietic stem cells. The hematopoietic stem cell has two characteristics which are the pluripotentiality or capacity to give rise to different hematopoietic cell strains and the self-renewal or property of self-perpetuation, generating cells the same as its self (Weissman I L et al., 2000). This capacity is essential for the maintenance of hematopoiesis throughout the life which, without self-renewal, would quickly exhaust the reserve of available stem cells. Hematopoietic stem cells are capable of generating different mature hematopoietic cell types through a series of intermediate progenitors and precursors. These progenitors and precursors suffer an ordered sequence of events which transform them into mature cells. This process is known with the name of differentiation (Lee M F et al., 2005). The differentiation of the hematopoietic cells involves changes which affect, among others, the size and form of the cell, gene expression, proteins, response to signals and localization of the cells. 
         [0005]    The terminally differentiated cells have lost their capacity for division and suffer apoptosis after a period of time which goes from hours for neutrophils to decades for some lymphocytes. This fact means the B.M. should constantly ensure cell exchange (Datta S R et al., 1999). 
         [0006]    The hematopoiesis process comprises a complex interaction between intrinsic genetic events of the hematopoietic cells and environment wherein they are found. This interaction is that which determines if the hematopoietic precursors and progenitors must stay quiescent, proliferate, be differentiated in one or another line or enter into apoptosis (Domen J et al., 1999). All the genetic and environmental mechanisms which govern the production of blood cells operate by altering the relative balance of these fundamental cell processes. 
         [0007]    Environmental and genetic factors are critical in hematopoiesis. Thus, for example, the gene expression belongings to the Rb families (Bergh et al., 1999), cyclins (Della Ragione F et al., 1997) or Hox (Magli M C et al., 1997) regulate the proliferation of hematopoietic cells at early stages of differentiation. The genes of the bcl-2 family regulate apoptosis in hematopoietic cells (O&#39;Gorman D M et al., 2001). A great variety of genes among which are found C/EBP (Tenen D G et al., 1997), Pax5 (Nutt S L et al., 1999) and lkaros (Nichogiannopoulou A. et al., 1998) seem to be involved in hematopoietic differentiation and line compromise. 
       Hematological Neoplasias 
       [0008]    Hematological neoplasias are malignant processes which affect any one of the cell types involved in the hematopoietic system. As a consequence of this transformation, the cell is blocked in a stage of differentiation and starts to accumulate due to uncontrolled proliferation, to a failure of the apoptotic mechanisms or a blocking of its differentiation process. 
         [0009]    The malignant transformation of the hematopoietic cells during the different stages they pass through in their differentiation to mature cells originates a great number of different neoplasias (Guttmacher A E et al., 2003). This type of neoplasias is therefore a very heterogeneous group of diseases which only has the hematopoietic origin of the cell type transformed in common. 
       Classification of Hematological Neoplasias 
       [0010]    Generically, it is possible to establish two groups: lymphoid neoplasias which affect the different cell type and degrees of maturity which form the lymphoid line, both B and T, and the other large group is constituted by the myeloid neoplasis which affect various cell types of the myeloid line. However, this simplistic classification is currently more developed, as detailed below. 
         [0011]    From a clinical standpoint, classically, lymphoma leukemias have been differentiated in arbitrary form, indicating the leukemias as those neoplasias which affect the bone marrow and have peripheral expression, i.e. circulation of anomalous cells in blood, and lymphomas as those neoplasias which remain localized in the lymph nodes or other lymphoid tissues and which lack, at least initially, leukemic behaviour. In the case of leukemias, the acute processes of the chronics has initially been differentiated by the morpho-cytological characteristics of the proliferating cells (immature and atypical in the first case and differentiated in the second) and to the clinical manifestations of the disease. At present, the knowledge of the immunological markers and the genetic alterations which affect the hematopoietic cells help to differentiate the different processes more accurately. 
         [0012]    Today, it is known that hematological neoplasias, as occurs in other types of cancer, have a multigenic origin. The great technological revolution produced in recent years has made it possible to know the molecular basis of several neoplasias. The use of these techniques makes it possible to identify relevant genes in human cancer, confirm the results obtained in basic research in animal models, establish patters of susceptibility, more accurately classify the neoplasias, improve the diagnosis of the disease, identify new therapeutic targets and improve the therapeutic selection for each patient. 
         [0013]    Also, the diversity which exists between individuals is important and has its clinical repercussion, based on the genetic differences: if we are capable of recognising these genetic differences, we will also be capable of advancing in discovering toxicity and differences in response to treatment. (Westbrook C A et al., 2005). 
         [0014]    In 1995, the World Health Organization (WHO) in collaboration with the European Hematology Association and pathologists, clinicians and scientists throughout the world, started a project in order to obtain an agreed classification of the hematopoietic tissue and lymphoid organs. This project led to the development of a system for the definition, classification and establishment of agreed diagnostic criteria for myeloid, lymphoid and histiocytic neoplasias (Jaffe E S et al., 2001). The classification criteria of the WHO are the same used in the REAL (Revised European American Lymphoma) classification published by the International Lymphoma Study Group in 1994 (Harris N L et al., 1994). The REAL classification system, unlike other previous classification systems is based on the definition of “real” entities and not morphological subtypes. All available information is used to establish these “real” entities, i.e. morphological, immunophenotypical and biological data are combined with the genetic and clinical characteristics (Harris N L et al., 1999a). 
         [0015]    The WHO classification, which was presented in 1997, stratifies the entities in accordance with the cell line affected: myeloid, lymphoid, histiocytic/dentritic and mastocytic. Within each category, the disease is defined in accordance with the morphology, immunophenotype, genetic and clinical data (Harris N L et al., 1999b). In many neoplasias, the stage wherein the accumulated tumour cell is found does not coincide with the stage in which the initial transformer event has occurred. Thus, many hematological neoplasias originate in the initial precursors and the specific genetic alteration may determine which cell continues advancing in its differentiating until stopping and accumulating in more advanced stages of differentiation (Shaffer A L et al., 2002). In contrast, other neoplasias can develop in the more advanced stages of differentiation, as occurs in the cells from the follicular centres wherein the genetic translocations and rearranging produce activation of genes which contribute to tumour development. The classification for each entity reflects the best stimulation for its cell line and stage of differentiation, recognising that the knowledge available at present is imperfect and that changes may occur in the assignment to a cell line and in classification as the available knowledge improves. 
         [0016]    The current criteria of diagnosis and classification of these neoplasias are based on a combination of (Braziel R M et al, 2003):
       Morphological evaluation of the cell: Observation under the microscope of the cells involved. Information is obtained on the type of cell and degree of its maturity.   Study of the immunophenotype: Recognition of antigens expressed on the surface of the neoplastic cell. These antigens are expressed differently and to different degrees in accordance with the line and of the stage the cell is at. The expression of surface antigens characteristic of the line and stage of differentiation of the cell is known, for example, the expression of CD19 and CD20 is typical of line B cells, whilst the expression of CD3 is typical of line T. The study of CD23 is key when differentiating NHLCM from CLL (Gong J Z et al., 2001).       
 
         [0019]    An attempt has always been made to relate the different types of neoplasias with their corresponding normal cell population through their morphological and immunophenotypical characteristics. Many neoplasias therefore seem “trapped” in determined stages of development as they have morphological and immunophenotypical characteristics similar to those of the hematopoietic cell at that stage of differentiation (Shaffer A L, et al., 2002).
       Clinical characteristics: Signs and symptoms of the patient at the time of diagnosis.   Determination of molecular markers: Measurement of some molecules which are associated to concrete entities such as the presence of PMURARA in promyelocytic leukemia or which give a better or worse prognosis, such as, for example, the expression of CD38 in CLL cells marker of bad prognosis (Durig J et al., 2002)   Cytogenetic studies based on the search for genetic alterations in the DNA of tumour cells. In many cases, specific rearranging occur which are characteristic of types of tumour or stages (Mitelman F, et al., 1997). In accordance with the chromosome translocations, it is possible to establish different groups with clinical significance, for example, in LLA-B, where the presence of fusion oncoproteins is frequent, the presence of t(2;21)/TEL1-AML1 and t(1;19)/E2A-PBX1 is associated with a response to the treatment whilst the prognosis for patients with t(9;22)/BCR-ABL and t(4;11)/MLL-AF4 is much worse (Arico M et al., 2000). Searches are also usually made for specific mutations, deletions or insertions in a gene which have been related to more favourable prognosis such as, for example, the myelodysplastic syndromes associated to 5q- (Boultwood J et al., 1994).       
 
         [0023]    As has previously been commented, the WHO establishes four large groups of hematological neoplasias in accordance with the strain involved (myeloid, lymphoid, histiocytic/dentritic and mastocytic lines). Below the neoplasias belonging to the myeloid line and the lymphoid line are described in more detail as they are those which arise with greatest frequency. Those corresponding to the histiocytic/dentritic and mastocytic lines for the moment are very isolated entities. 
       1. Myeloid Neoplasias 
       [0024]    They group together all the neoplasias originated in the myeloid line of differentiation, the WHO distinguishes four large groups (Vardiman J W et al., 2002). 
         [0025]    1.1 Myeloproliferative Syndromes (MPS) 
         [0026]    Myeloproliferative syndromes (MPS) are clonal alterations of the hematopoietic stem cell characterized by effective hematopoiesis which leads to an increase in the blood levels of one or more hematopoietic and hepatosplenomegaly lines. They constitute a group of entities wherein there exists an increase in precursors of the myeloid series or fibrosis of the bone marrow (myelofibrosis); this group also includes systemic mastocytosis. The following can be highlighted:
       Chronic myeloproliferative syndromes (CMPS). Clonal alteration of the hematopoeietic stem cell. Characterized by an effective hematopoiesis which produces increase in peripheral blood of one or more cell lines and frequently hepatosplenomegaly, medullary hypercellularity with maturity but without dysplasia.   Chronic myeloid leukemia (CML). It is a clonal process secondary to an acquired genetic alteration of the pluripotent cell. The disease is characterized by the superproduction of neu trophils and of their precursors. It has three phases: the first called chronic phase of undefined duration, followed by the acceleration phase and finally the blastic crisis which is really secondary acute leukemia.       
 
         [0029]    CML has a low incidence of approximately one case per 100,000 inhabitants/year and appears most frequently in the sixth and seventh decades of life. It can be considered a rare disease. 
         [0030]    It is the characteristic leukemia par excellence as the term leukaemia was applied to this entity for the first time. 95% of the cases have a genetic marker, the Philadelphia chromosome, originated by the translocation of a fragment of chromosome 22 which adheres to chromosome 9 or t(9;22) (q34;q11). This translocation causes the fusion gene bcr-abl. The protein coded by this chimeric gene, BCR-ABL, has an increased thyrosine-kinase activity compared with the normal abl protein activity as oncogenic growth factor (Pane F et al., 2002), although really the mechanisms which produce the superproduction of myeloid cells are not totally clarified. It is possible that other proto-oncogenes such as p-53 intervene in the process and in the transformation of chronic phase to blastic crisis. The few cases in which the Philadelphia chromosome is detected represent atypical myeloproliferative symptoms and correspond to the variant of MDS known as chronic myelomonocytic leukemia (CMML). 
         [0031]    The diagnosis is based on the high cell counts for the blank series, appearance of morphologically normal myeloid cells and in all the stages of differentiation, but with a high number of myelocytes and neutrophils, there are generally basophilia and thrombocytosis. In the acceleration phase an increase in immature cells occurs in the peripheral blood and in the blastic crisis the predominant cell is the myeloblast (65%) or the lymphoblast (35%).
       Vaquez&#39;s disease (VD). It is the myeloproliferative syndrome characterized by the increase in mass of the red series. Vazquez&#39;s disease is a benign haematological disease, whose suffering does not influence shortening of survival. However, it is a clonal disease which may evolve in 15% of patients to myelofibrosis or acute leukemia (5%).   Essential Thrombocythemia (ET). Myeloproliferative syndrome characterized by platelet production 15 times greater than normal. It may be associated to thrombotic or hemorrhagic complications secondary to platelet dysfunction. It appears at around 60 years of age, with equal incidence in both sexes.   Myelofibrosis (MF). It is a neoplastic clonal disorder of the pluripotent stem cell. It is characterized by a great production of abnormal megakaryocytes. These cells release molecules (growth factor derived from platelets, platelet factor 4) which stimulate the proliferation of fibroblasts and build collagen fibres in the bone marrow. The bone marrow is incapable of functioning normally and the hematopoietic precursor cells translate to the liver and spleen, giving rise to extramedullary hematopoiesis. Characterized by fibrosis of B.M and splenomegaly. It appears in people over 50 years of age and has no preference of sex.       
 
         [0035]    Mastocytosis. Group of entities characterized by the proliferation of mastocytic cells in different parts of the body. Systemic mastocytosis (SM), is a rare disease which typically affects adults and has bone alterations in 70% of patients (Chen C C et al., 1994). 
         [0036]    1.2. Myelodysplastic/Myeloproliferative Syndromes (MDS/MPS) 
         [0037]    The WHO has established a somewhat different classification, separating MDS/MPS as entities differentiated from the other MDS, since they share characteristics with the CMPS that make them different. This group includes three entities: chronic myelomonocytic leukaemia, chronic atypical myeloid, leukeumia, juvenile myelomonocytic leukaemia and non-classifiable MDS/MPS. Myelodysplastic syndromes (MDS) are clonal proliferations of the hematopoeietic stem cell which share at the time of diagnosis, clinical, morphological and analytical data which are superimposed between AML and CMPS. They are characterized by the hypercellularity of bone marrow due to the proliferation of one or more myeloid lines (Heaney M L, 1999). The presence of dysplasia in at least one line (myeloid, erythroid or megakaryocytic-platelet) is a characteristic of MDS. The incidence is variable depending on the variety. An incidence of 3 cases×100,000 inhabitants over 60/year is estimated. The FAB classification establishes 4 diagnostic categories (Bennett J M et al., 1984): simple refractory anemia (RA), refractory anemia with ring sideroblasts (ARS), refractory anemia excess blasts (RAEB) and refractory anemia with excess blasts in transformation (RAEB-T) and chronic myelomonocytic leukemia (CMML). 
         [0038]    With regard to the MDS, the WHO establishes five differentiated categories (Harris N L, et al., 1999): refractory anemia, refractory cytopenia with multiline dysplasia, refractory anemia with excess blasts, non-classifiable MDS and MDS associated to an isolated defect in chromosome 5 (of the 5q) or syndrome 5q-. 
         [0039]    1.3. Acute Myeloblastic Leukemia (AML) 
         [0040]    Clonal proliferation of immature cells of the myeloid line. They may appear de novo or secondary in patients with myelodysplastic syndrome (MDS). The classification prepared by the French-American-British group (FAB) considers eight varieties (M0-M7) based on morphological criteria and on the immunophenotype of the neoplastic cells (Bennett J M, et al., 1976). Despite the fact that this classification has been accepted for many years, the discovery that many genetic alterations have a predictive characteristic and the incorporation of the cytogenetic analysis to the diagnosis of acute leukemias (Bene M C et al., 2001) has made it possible to subclassify the disease and establish the evaluation of the prognosis, as occurs with translocation t(15;17) which characterized promyelocytic variety leukemia which is characterized by the expression of a retinoic acid receptor (RAR), characteristic which makes this type of leukaemia sensitive to treatment with transretinoic acid (TRA) in most cases. 
         [0041]    The WHO classifies AML by incorporating morphological, immunophenotypical, genetic and clinical data to be able to define biological homogeneous entities and with clinical relevance. Thus, AML is classified into four large categories: 1.—AML with recurrent genetic anomalies. 2.—AML with multiline dysplasia. 3.—AML related to treatment and 4.—non-classifiable AML (ref WHO). The three first categories recognise the importance of biological factors which predict the evolution of the process. The cytogenic analysis represents the most powerful prognosis factor (Roumier C, et al., 2003). It is used to identify subgroups of AML with different prognosis: low risk with favourable response to treatment (t(8;21), t(15;17) or inv(16)), intermediate risk (normal karyotype or t(9;11) or high risk (inv(3), −5del(5q) or −7del(7q), or more than three alterations). There is molecular heterogeneity within the risk group. In some cases of patients with normal karyotype, the presence of mutations has been found in gene FLT3 (Kottaridis P D, et al., 2001.) and MLL (Dohner K et al., 2002). 
         [0042]    The medullary image in the microscopic examination of aspirate is generally that of invasion by cells similar to one another, of immature morphological characteristics which distort the normal cell distribution constituting authentic cell sheets. Medullary hyperproduction conditions which areas of inactive bone marrow come to again present a new focus of hematopoiesis in the adult age, in this case of abnormal cells. 
         [0043]    Approximately 80-90% of young patients with AML, achieve complete remission of the disease after chemotherapy. However, the majority relapses, and a cure occurs in 30%. The oncogenic transplant of bone marrow has managed to increase the cure rate to 50%, but it is limited by the availability of identical donor HLA. It is therefore a group of neoplasias with diverse genetic abnormalities and variable response to treatment (Giles F J et al., 2002) 
       2. Lymphoid Neoplasias 
       [0044]    The WHO&#39;s classification is a refinement of the REAL classification (Harris N L et al. 1994). Three large groups of lymphoid neoplasias: 1.—Lymphoid neoplasias derived from B cells. 2.—Lymphoid neoplasias derived from T and NK cells. 3.—Hodgkin&#39;s lymphoma. This classification includes solid neoplasias and lymphoid leukemias, as in many of them their occurs a transformation from one phase to another and the distinction between them, may be artificial. Thus, chronic lymphatic leukemia B and the lymphocytic NHL are originated by the same cell and represent different manifestations of the same neoplasia, the same occurs with lymphoblastic lymphoma and lymphoblastic leukemia 
         [0045]    2.1. Neoplasias Derived from B, T and NK Cells 
         [0046]    The WHO&#39;s classification divides these neoplasias in accordance with the stage of maturity of the cells in neoplasias of precursor cells and neoplasias of mature cells (WHO Classification Tumours of Haematopoietic and lymphoid tissues. In Pathology and genetics of tumours of Haematopoietic and lymphoid tissues. E S Jaffe, N L Harris, H Stein, J W Vardiman. IARC Press. Lyon, 2001). Due to the high number of entities described, the following are highlighted:
       Acute lymphoblastic leukemia (ALL): Clonal proliferation of lymphoid precursors. In approximately 80% of the cases, the precursors belong to the lymphoid B line. The molecular analysis of the genetic alterations of the leukemic cells have significantly contributed to the understanding of the pathogenesis and prognosis of ALL (Ferrando A A et al., 2005). Despite the fact that the frequency of genetic subtypes differs in children and in adults, the general mechanisms which lead to ALL are a consequence of the abnormal expression of proto-oncogenes due to chromosome translocations which create fusion genes or a hyperploidy. This initial oncogenic event is probably insufficient to produce leukemia and it is believed that other alterations which cooperate with this first one are necessary to definitively alter the proliferation and survival of the transformed cell. All these alterations contribute to the leukemic transformation of the hematopoietic stem cells or of their progenitors as they affect key regulating processes, maintaining or increasing their capacity for self-renewal, escape from the normal proliferation controls, blocking of differentiation and promoting resistance to apoptotic signals (Hanahan D, et al., 2000).       
 
         [0048]    The overall appearance of the bone marrow is similar to that described for myeloid leukemia. The research of the minimal residual disease is important, a factor which condiciona with su presence the probable relapse of the disease. The FAB classification defines 3 stages in accordance with the morphology (L1-L3). 
         [0049]    It is the most frequent leukemia in the childhood, and in the clinical course and the response to treatment depends on the type of genetic alteration, for example, patients with hyperdiploidy have a favourable prognosis when it is treated with treatment schemes which include antimetabolites but, in general terms, children are cured with standard chemotherapy and prophylaxis of the CNS and in adults only 20% have prolonged survival with chemotherapy, the allogenic autologous transplant is useful for cases considered high risk.
       Chronic lymphatic leukemia (CLL). CLL is characterized by clonal proliferation and accumulation of lymphocytes with mature appearance and resistant to apoptosis in B.M, blood and lymphoid organs (Galton D A, 1966). When the lymphodenopathy is dominant, the clinical symptoms are called Lymphocytic lymphoma. The lymphocytes affected are line B in 95% of the cases and 5% of the cases involve T lymphocytes.       
 
         [0051]    It is the most frequent leukemia in the Western world. The average age of patients diagnosed is 65 years old, only 10-15% of the cases arise under 50 years (Jemal A et al., 2003). It is the most common cause of leukaemia in adults of the counties of the Western world and involves around 25% of all leukemias. The incidence is 3 cases per each 100,000 inhabitants and year, with a predominance in males, with a male/female proportion of 1.7:1. In recent years, it has increasingly been diagnosed in younger patients. The proportion of cases diagnosed at early stages of the disease (Rai K R, et al., 1975) has increased from 10 to 50%, probably due to an early diagnosis thanks to routine lymphocyte counts. The disease affects more men than women. 
         [0052]    The prognosis and clinical course of the disease is extremely variable. Some patients have a rapidly progressive evolution and die in the 2-3 years after the diagnosis, whilst in others, the course is indolent and they live for 10-20 years without problems related to the CLL. Intermediate cases occur in half of patients. 
         [0053]    Approximately, 20% of patients are asymptomatic at the time of diagnosis, performing this as a consequence of a routine blood analysis. When symptoms exist, they are not specific and include fatigue, weakness and discomfort. 
         [0054]    The Binet classification (Binet J L et al., 1981) defines 3 stages of disease in accordance with the concentration of haemoglobin, number of platelets, number of lymph nodes involved and the presence of visceromegalies. The Rai classification (Rai K R et al., 1975) uses the same indicators but classifies patients in five groups. 
         [0055]    This neoplasia is not characterized by a unique and recurrent genomic alteration. There are some markers which give a more unfavourable prognosis such as the presence of deletions in chromosomes 17 and 11 and those patients with absence of mutations in IgVh genes (40% of the cases) and high proportion of cells expressing CD38 is characterized by a more agressive clinical course and a worse response to treatment (Hamblin T J et al., 1999; Durig J et al., 2002). Another recently described marker is ZAP-70, independent prognosis marker whose expression is indirectly related to the mutational state of the gene of the heavy chains of immunoglobulins (Crespo M et al., 2003).
       Multiple myeloma: MM). MM is a malignant disease wherein a clone of plasma cells (terminal cells of the B lymphoid line) of the bone marrow suffers uncontrolled proliferation. It involves 10-15% of all the malignant diseases and is characteristic of advanced ages, only 2% of the cases are diagnosed before 40 years of age. For unknown reasons, the incidence of the disease is increasing.       
 
         [0057]    These cells produce and secrete monoclonal immunoglobulin or fragments of immunoglobulins, composed by a heavy and light chain class (kappa or lambda). Occasionally, the myeloma cannot be secreted or the protein is not detectable in serum or urine. The neoplastic plasma cell produces other molecules such as IL6, tumour necrosis factor or osteoclast activator factor which contributes to producing osteolysis, hypercalcemia and renal insufficiency, characteristics alterations of the disease. 
         [0058]    The diagnosis can be casual on performing an analysis in patients without symptomology or limited disease (20% of cases). The disease in these patients can remain stable for years and early treatment in the asymptomatic phase does not provide any advantages. 
         [0059]    Patients with monoclonal component but which do not meet the MM diagnosis are considered carriers of monoclonal gammapathy of indeterminate meaning (MGIM). Among 10 and 20% of these patients develop MM in 10 years (Kyle R A, 1997; Zhan F et al., 2002). The monoclonal component can also be associated to other diseases such as lymphoma, non-hematological neoplasias and diseases of the connective tissue.
       Lymphoplasmocytoid lymphoma and Waldenstrom&#39;s macroglobulinemia. It is the clinical expression of a low-degree lymphoproliterative disease, characterized by the infiltration of anomalous lymphoplasmocytic cells in bone marrow, lymph node and spleen, accompanied by monoclonal production of immunoglobin M, which conditions an increase in blood viscosity and the appearance of haemorrhagic vascular manifestations and by difficulty in circulation in the small vessels.   —Non-Hodgkin&#39;s lymphoma (NHL). NHL are solid tumours of the lymphoid tissue which are much more heterogeneous than Hodgkin&#39;s disease. The complexity and diversity of the NHL as regards morphology, genetics, phenotype and clinical behaviour has given rise to the existence of multiple classifications, none of them completely satisfactory.       
 
         [0062]    It is the most frequent hematological disease and, in terms of years of life lost, it is the fourth most important neoplasia of the Western world and it seems that its incidence is increasing. 
         [0063]    It may appear at all ages, but the average appearance is 50 years of age. The cause of the disease is not clear. Specific chromosome translocations have been described associated to certain types of lymphomas, for which reason they are of great use in diagnosis (Montoto S et al., 2003). Most of the Burkitt-type lymphomas present translocation t(8;14), wherein the c-MYC oncogene of chromosome 8 is transferred to the next region in chromosome 14 where the heavy immunoglobins chains are coded. 90% of ollicular lymphomas are characterized by translocation t(14;18), where the bcl-2 gene of the chromosome 18 is transferred to the region of the heavy immunoglobulin chains. It is well known that the overexpression of bcl-2 inhibits apoptosis (programmed cell death). It is easy that this chromosome rearranging requires other stimulation, such as, for example, the coexpression of a second proto-oncogene or an antigenic stimulation to develop the malignant proliferation. An example of combination of multiple combined causes constitute the lymphoma associated to AIDS. The appearance of aggressive extranodal lymphomas is the result of the combination of immunosuppression by HIV, deregulation of a proto-oncogene (c-MYC) and a secondary viral infection (Epstein-Barr&#39;s virus), the same occurs in patients subjected to organ transplant (Harris N L et al., 2001). 
         [0064]    The clinical presentation of the disease is more irregular than in Hodgkin&#39;s disease. It may behave indolently without requiring immediate treatment or, in contrast, behave aggressively which is quickly fatal. 
         [0065]    The most frequent nodal condition is cervical. As regards extranodal condition, the signs and symptoms depend on the affected organ. The bone marrow appears infiltrated with greater frequency in the low degree NHL and may cause pancytopenia. The presence of malignant cells in peripheral blood is also frequent in low-degree NHL, but of very bad prognosis in those of high-degree. 
         [0066]    The diagnosis is carried out by the histological study of the lymphatic tissue. The additional information is obtained by monoclonal antibodies directed against specific lymphocytic antigens (immunophenotype); this helps to identify the degree of maturity of the malignant cell and determine the T or B origin thereof. The presence of mutation in genes which code Ig in the NHL of strain B are usually used for the identification of some subtypes of NHL (Kuppers R et al., 1999). 
         [0067]    2.2. Hodgkin&#39;s Lymphoma (LH) 
         [0068]    It is an infrequent disease and has predilection for the masculine sex in a proportion of 2/1. It is characterized by the presence of large cells, bi or multi-nucleus called Reed-Sternberg (RS) and other smaller and mononuclear cells which appear in a small quantity in the tumour; the rest of the cells are lymphocytes, granulocytes, fibroblasts and plasma cells. This inflammatory infiltrate probably reflects the immune response of the host with the malignant cells. The nature of the RS and Hodgkin&#39;s cells have been greatly studied but continues being disputed. They may be derived from an initial stage of the lymphoid cells. 
         [0069]    In some cases, the existence of DNA for Epstein-Barr&#39;s virus has been detected in the tumour. One hypothesis is that the bimodal distribution of the disease is due to the infection in young subjects and the other peak would be caused by average environmental causes. 
         [0070]    The diagnosis is obtained by biopsy of a lymph node. To plan the treatment, it is necessary to determine the extension of the disease. (Küppers R, 2002; Cossman J, 2001; Devilard E et al., 2002). 
       Problems in Classification 
       [0071]    The great quantity of hematopoietic cells and the many stages of differentiation through which they pass further complicates the classification of the neoplasis originating from this type of cells. Despite the efforts to establish a classification based on “real” entities, some of the categories are ambiguous and in many cases contain very heterogeneous groups as regards a response to therapy of clinical course. This heterogeneity is that responsible for, on the one hand, the incessant search for markers capable of differentiating some behaviours from others and, on the other hand, that the disputed classification of this type of neoplasis is subjected to continuous revisions. 
         [0072]    An ideal classification system should be precise, reproducible, easy to use and should especially have biological and clinical significance (Chan W C, et al., 2005). The current diagnosis systems and the classification of the hematological neoplasias are based on the recognition of histological and morphological, immunophenotypical and cytogenetic characteristics and study of a molecular marker with prognostic value. However, in some of the diagnostic categories defined in this way, the following is observed:
       A marked heterogeneous therapy response. Within the same disease there are patients who reach full remission, partial remission, do not respond, which relapse after a certain therapy. The capacity to predict a response is especially important in this type of neoplasis since the transplant of stem cells is an effective but toxic alternative response. The capacity to determine what patients would respond to a conventional therapy before giving it may be beneficial to be able to apply the most effective treatment to each patient.   A variable clinical behaviour. Within this category there are patients whose disease is going to remain stable for long periods of time and which are not going to need therapy and those whose disease is going to progress rapidly requiring aggressive therapy.       
 
         [0075]    These variations point to the existence of molecular heterogeneity within the diagnostic categories, differences which the conventional methods of diagnosis are not capable of determining and hence, the search for new forms of analysis which provide a greater resolution in the characterization of this type of neoplasias. 
         [0076]    In this line, the use of expression arrays have demonstrated being effective not only in deciphering the biological and clinical diversity which is found in many tumours, but in understanding the biological and pathological processes which affect many symptoms and, in particular, the hematopoietic system. The expression arrays are ordered arrays of sequences associated to a solid support, complementary to mRNA or to its corresponding cDNA or cRNA, which allow the analysis of the differential expression of hundreds or thousands of genes simultaneously. One of the supports to which they are frequently bound is to rectangular fragments of glass similar to slides, a format which is frequently alluded to by the terms microarray, biochip or, simply, chip. Their use is becoming increasingly frequent for the diagnosis of various diseases or for the evolution of the evaluation of the susceptibility of suffering from them. 
       First Works of Arrays and Hematological Neoplasias 
       [0077]    In 1999, the Golub group published one of the first articles referring to the role of arrays in the classification of hematological neoplasias (Golub T R et al., 1999). An array with 6817 genes represented was used for the study of expression profiles in AML and ALL. A group of 50 genes was selected with the capacity of predicting the type of leukemia (class predictor) and they were used to classify a group of unknown samples in the correct categories. The study of the expression of these 50 genes is sufficient for the classification of a sample of acute leukemia in AML or ALL. Despite the fact that the distinction between AML and ALL is well established with the current diagnostic methods, the study revealed the existence of specific expression patterns associated with each type of acute leukemia and proved the use of expression profiles in cancer classification. 
         [0078]    In 2000, the Alizadeh group published an article in which a specialized array is used, the lymphochip which contains genes expressed preferentially in lymphoid cells or if which an immunological or oncological importance is known with 17,856 sequences (Alizadeh A A et al., 1999). This group used the “lymphochip” for the study of gene expression patterns associated to differences in clinical behaviour in a Diffuse Large B-Cell Lymphoma (DLCL) (Alizadeh A A, et al. 2000). The DLCL is a NHL with a very heterogeneous behaviour and impossible to distinguish using conventional diagnostic methods: 40% of patients respond well to therapy and have prolonged survival whilst 60% die due to the disease. The authors found that the gene expression could be related to the clinical behaviour of the tumours. This was one of the first articles to speak of arrays for the “subclassification” of hematological neoplasias, i.e. the use of expression profiles for the identification of two different groups of DLCL from the transcriptional standpoint, DLCL subtypes with clinical behaviour impossible to predict with conventional diagnostic criteria. 
         [0079]    At present there are multiple publications wherein, directly or indirectly appear the arrays applied not only to classification and subclassification, but also to the study, diagnosis, prognosis, identification of new markers in haematological diseases (Greiner TC, 2004; Alizadeh A A et al, 2000; Bea S et al., 2005; Dave S S et al., 2004), as well as patent applications which disclose the use of this type of device for the differentiation between different types of hematological neoplasias. Thus, for example, patent application WO2003/008552 discloses the use with diagnostic purposes of differences in the expression pattern of genes to differentiate between mixed line leukemia (MLL), acute lymphoblastic leukemia (ALL) and acute leukemia myelogenous leukemia (AML), defending the possibility of making this differential diagnosis with the data obtained after the diagnosis of samples from patients afflicted by each one of these types of leukemia by the use of commercial chips from Affymetrix. Although genes are indicated with variations in the expression between the three types of leukemias which would permit the differentiation between them, no specific sequences are mentioned other than those present in the Affymetrix chip which could have been used to detect these genes by devices different from those of said company, nor does it consider the design of devices or methods which would permit the diagnosis of other types of leukemias or, in general, neoplasias derived from hematopoietic cells. 
         [0080]    Patent application WO2005/024043, for its part, also relates to the field of gene expression analysis to go into greater detail in the knowledge of differences existing at a molecular level between the different neoplasias derived from hematopoietic cells, specifically centering on the case of lymphomas, to extract data which help in its diagnosis or in the prognosis of its evolution. In particular, it discloses a method to obtain useful functions to predict the evolution of individuals affected by different types of lymphomas evaluating in lymph node biopsies to what extent patterns or genetic prints contribute in each one of them, groups of genes which are expressed in a coordinated manner and which are related to the cell origin of the neoplasia, the different types of non-malignant cells present in the biopsy and the oncogenic mechanisms responsible for cancer. The different patterns or genetic prints are also deduced in this case from the data obtained with commercial chips from Affymetrix. Furthermore, application WO2005/024043 states it provides an alternative microarray, composed of a fewer number of sequences than the Affymetrix microarrays, which would also permit the analysis of differences in gene expression between lymphomas and their application for deducing functions of prediction of survival and for the differentiation between different types of lymphomas. Although it indicates the genes whose analysis would be made possible by that microarray, the specification of application WO2005/024043 does not indicate the sequence of the probes which would compose the microarray, only mentioning that they would be cDNA type and leaving doubts over whether that cDNA would appear complete or the analysis of the corresponding gene expression would be carried out using as probe only one fragment of said cDNA, which would remain tp be determined. 
         [0081]    It would be interesting to have compositions and methods which would permit ifferentiation between neoplasias of hematopoietic origin based on their molecular level difference, specifically designed for this group of neoplasias, wherein it would evaluate the expression of a more reduced number of genes than in the commercial microarrays used in the studies described in the aforementioned patient applications and which enabled both the diagnosis of certain neoplasias and the prediction of their future evolution, thus helping in the prescription of a suitable treatment for each patient, a particularly interesting characteristic in those neoplasias, as is the case of CLL, wherein the prognosis of the future evolution of the patient is difficult with the knowledge and tests available to date. Furthermore, it would be particularly convenient that the probes used to evaluate the expression of the expressed genes had been designed specifically so that, in addition to being specific and with a perfectly defined sequence, all had a similar behaviour, which would make them suitable, in general, to use in combination in a same test and, in particular, to form part of the same ordered array associated to a solid support, such as chips or microarrays. The compositions and methods of this invention meet this need. 
         [0082]    Instead of commercial microarrays to detect genes significant for distinguishing between neoplasias or creating functions which predict the survival of the individual suffering from it, the invention provides new oligonucleotides, of perfectly defined sequence, capable of specifically detecting genes which have been selected as they are known to be significant for the biology of blood cells or for the pathology of different neoplasias, oligonucleotides which also have the feature of having being designed so that they share common characteristics which have a similar behaviour to those used as probes in hybridization, which makes them suitable to be used in compositions which comprise combinations thereof. Said compositions and in particular those wherein these nucleotides are arranged in ordered form on an easy to handle solid support such as glass similar to slides, are suitable for carrying out tests to detect statistically significant genes or differentiate samples taken from individuals suffering from certain types of neoplasias originating from hematopoietic cells of samples taken from individuals not suffering from said neoplasias, as they are compositions which contain a number of nucleotides less than those commercial microarrays designed with a more general purpose, being specifically designed for the analysis of samples from individuals suffering from neoplasias and composed of a known sequence of probes, perfectly reproducible, which are designed to be used together in the same test as they are of similar behaviour. The additional inclusion in the microarrays of the invention of oligonucleotides of low homology with human genes, but chosen so that the rest of their characteristics are similar to those of the oligonucleotides of the invention designed to act as probes capable of recognizing human genes with high specificity, permits the use of said microarrays for the identification of statistically significant genes in the identification of samples associated to certain neoplasias of hematopoietic origin by the use of tests wherein it is feasible to establish controls in all their phases. As shown in the examples which appear further on, in the present specification the use of these microarrays in combination with various statistical techniques permits the correct classification of different biological samples by a method which is precise, reproducible, easy to use and with biological and clinical significance, as they are based on differences of gene expression with significance for the biological processes which are being analysed. In particular, the use of a microarray of the invention in combination with the method of the invention permits the identification of blood samples in patients suffering from chronic lymphatic leukemia (alteration not considered in applications WO2003/008552 and WO2005/024043 and whose diagnosis has not been described by the use of commercial microarrays), distinguishing those of both samples obtained from healthy individuals and samples related to other types of leukemias, and those corresponding to Jurkat or U937 cells, facilitating the diagnosis of CLL through the analysis of expression levels of statistically significant genes to do this and even permitting the obtainment of functions which enable the mathematical calculation of the probability of a sample belonging to individuals afflicted with stable chronic lymphatic leukemia from samples belonging to individuals afflicted with progressive chronic lymphatic leukemia, a distinction which is now difficult to carry out a priori by the available techniques, which means it is a useful and novel tool for the prognosis of the future evolution of individuals afflicted with this disease, individuals whose diagnosis may also have been carried out by compositions and method of the invention or may have been known thanks to the application of a different method, but for which, on having a tool which makes it possible to make a prognosis on how the CLL they are suffering from is going to later evolve, it would be easier to decide if it is suitable to subject them to an immediate aggressive treatment or simply keep them under observation to check that their gene expression data continue indicating that the disease is going to remain stable for a long period of time. 
       SUMMARY OF THE INVENTION 
       [0083]    The invention provides compositions which include at least one oligonucleotide from the group composed of: 
         [0000]    SG1, SG2, SG3, SG4, SG5, SG6, SG7, SG8, SG9, SG10, SG11, SG12, SG13, SG14, SG15, SG16, SG17, SG18, SG19, SG20, SG21, SG22, SG23, SG24, SG25, SG26, SG27, SG28, SG29, SG30, SG31, SG32, SG33, SG34, SG35, SG36, SG37, SG38, SG39, SG40, SG41, SG42, SG43, SG44, SG45, SG46, SG47, SG48, SG49, SG50, SG51, SG52, SG53, SG54, SG55, SG56, SG57, SG58, SG59, SG60, SG61, SG62, SG63, SG64, SG65, SG66, SG67, SG68, SG69, SG70, SG71, SG72, SG73, SG74, SG75, SG76, SG77, SG78, SG79, SG80, SG81, SG82, SG83, SG84, SG85, SG86, SG87, SG88, SG89, SG90, SG91, SG92, SG93, SG94, SG95, SG96, SG97, SG98, SG99, SG100, SG101, SG102, SG103, SG104, SG105, SG106, SG107, SG108, SG109, SG110, SG111, SG112, SG113, SG114, SG115, SG116, SG117, SG118, SG119, SG120, SG121, SG122, SG123, SG124, SG125, SG126, SG127, SG128, SG129, SG130, SG131, SG132, SG133, SG134, SG135, SG136, SG137, SG138, SG139, SG140, SG141, SG142, SG143, SG144, SG145, SG146, SG147, SG148, SG149, SG150, SG151, SG152, SG153, SG154, SG155, SG156, SG157, SG158, SG159, SG160, SG161, SG162, SG163, SG164, SG165, SG166, SG167, SG168, SG169, SG170, SG171, SG172, SG173, SG174, SG175, SG176, SG177, SG178, SG179, SG180, SG181, SG182, SG183, SG184, SG185, SG186, SG187, SG188, SG189, SG190, SG191, SG192, SG193, SG194, SG195, SG196, SG197, SG198, SG199, SG200, SG201, SG202, SG203, SG204, SG205, SG206, SG207, SG208, SG209, SG210, SG211, SG212, SG213, SG214, SG215, SG216, SG217, SG218, SG219, SG220, SG221, SG222, SG223, SG224, SG225, SG226, SG227, SG228, SG229, SG230, SG231, SG232, SG233, SG234, SG235, SG236, SG237, SG238, SG239, SG240, SG241, SG242, SG243, SG244, SG245, SG246, SG247, SG248, SG249, SG250, SG251, SG252, SG253, SG254, SG255, SG256, SG257, SG258, SG259, SG260, SG261, SG262, SG263, SG264, SG265, SG266, SG267, SG268, SG269, SG270, SG271, SG272, SG273, SG274, SG275, SG276, SG277, SG278, SG279, SG280, SG281, SG282, SG283, SG284, SG285, SG286, SG287, SG288, SG289, SG290, SG291, SG292, SG293, SG294, SG295, SG296, SG297, SG298, SG299, SG300, SG301, SG302, SG303, SG304, SG305, SG306, SG307, SG308, SG309, SG310, SG311, SG312, SG313, SG314, SG315, SG316, SG317, SG318, SG319, SG320, SG321, SG322, SG323, SG324, SG325, SG326, SG327, SG328, SG329, SG330, SG331, SG332, SG333, SG334, SG335, SG336, SG337, SG338, SG339, SG340, SG341, SG342, SG343, SG344, SG345, SG346, SG347, SG348, SG349, SG350, SG351, SG352, SG353, SG354, SG355, SG356, SG357, SG358, SG359, SG360, SG361, SG362, SG363, SG364, SG365, SG366, SG367, SG368, SG369, SG370, SG371, SG372, SG373, SG374, SG375, SG376, SG377, SG378, SG379, SG380, SG381, SG382, SG383, SG384, SG385, SG386, SG387, SG388, SG389, SG390, SG391, SG392, SG393, SG394, SG395, SG396, SG397, SG398, SG399, SG400, SG401, SG402, SG403, SG404, SG405, SG406, SG407, SG408, SG409, SG410, SG411, SG412, SG413, SG414, SG415, SG416, SG417, SG418, SG419, SG420, SG421, SG422, SG423, SG424, SG425, SG426, SG427, SG428, SG429, SG430, SG431, SG432, SG433, SG434, SG435, SG436, SG437, SG438, SG439, SG440, SG441, SG442, SG443, SG444, SG445, SG446, SG447, SG448, SG449, SG450, SG451, SG452, SG453, SG454, SG455, SG456, SG457, SG458, SG459, SG460, SG461, SG462, SG465, SG468, SG469, SG470, SG471, SG472, SG473, SG474, SG475, SG476, SG477, SG478, SG479, SG480, SG481, SG482, SG483, SG484, SG485, SG486, SG487, SG488, SG489, SG490, SG491, SG492, SG493, SG494, SG495, SG496, SG497, SG498, SG499, SG500, SG501, SG502, SG503, SG504, SG505, SG506, SG507, SG508, SG509, SG510, SG511, SG512, SG513, SG514, SG515, SG516, SG517, SG518, SG519, SG520, SG521, SG522, SG523, SG524, SG525, SG526, SG527, SG428, SG529, SG530, SG531, SG532, SG533, SG534, SG535, SG536, SG537, SG538, SG539, SG540, SG541, SG542, SG543, SG544, SG545, SG546, SG547, SG548, SG549, SG550, SG551, SG552, SG553, SG554, SG555, SG556, SG557, SG558, SG559, SG560, SG561, SG562, SG563, or combinations thereof. 
         [0084]    Said oligonucleotides have been designed so that, in addition to being specific for the corresponding genes whose expression one wants to evaluate, they have a similar behaviour, as they are of similar lengths and all of them have GC in the range of 40% to 60%, in addition to corresponding to zones situated less than 3000 nucleotides from end 3′ (poly(A)) of the mRNA which one wants to detect and evaluated and of being constituted by sequences which coincide in their sense with those of the corresponding mRNA. Therefore, they are suitable to be used in the same test or form part of a composition which comprises combinations thereof. A particular embodiment of the invention is constituted by the compositions which comprise mixtures of several of said oligonucleotides. Especially preferred are those compositions which comprise mixtures of oligonucleotides which correspond to genes significant for classifying a sample as associated to a certain neoplasia and/or to determine the future evolution thereof. Especially preferred embodiments of the invention are also those compositions which comprise the totality of the oligonucleotides from the group composed of: 
         [0000]    SG1, SG2, SG3, SG4, SG5, SG6, SG7, SG8, SG9, SG10, SG11, SG12, SG13, SG14, SG15, SG16, SG17, SG18, SG19, SG20, SG21, SG22, SG23, SG24, SG25, SG26, SG27, SG28, SG29, SG30, SG31, SG32, SG33, SG34, SG35, SG36, SG37, SG38, SG39, SG40, SG41, SG42, SG43, SG44, SG45, SG46, SG47, SG48, SG49, SG50, SG51, SG52, SG53, SG54, SG55, SG56, SG57, SG58, SG59, SG60, SG61, SG62, SG63, SG64, SG65, SG66, SG67, SG68, SG69, SG70, SG71, SG72, SG73, SG74, SG75, SG76, SG77, SG78, SG79, SG80, SG81, SG82, SG83, SG84, SG85, SG86, SG87, SG88, SG89, SG90, SG91, SG92, SG93, SG94, SG95, SG96, SG97, SG98, SG99, SG100, SG101, SG102, SG103, SG104, SG105, SG106, SG107, SG108, SG109, SG110, SG111, SG112, SG113, SG114, SG115, SG116, SG117, SG118, SG119, SG120, SG121, SG122, SG123, SG124, SG125, SG126, SG127, SG128, SG129, SG130, SG131, SG132, SG133, SG134, SG135, SG136, SG137, SG138, SG139, SG140, SG141, SG142, SG143, SG144, SG145, SG146, SG147, SG148, SG149, SG150, SG151, SG152, SG153, SG154, SG155, SG156, SG157, SG158, SG159, SG160, SG161, SG162, SG163, SG164, SG165, SG166, SG167, SG168, SG169, SG170, SG171, SG172, SG173, SG174, SG175, SG176, SG177, SG178, SG179, SG180, SG181, SG182, SG183, SG184, SG185, SG186, SG187, SG188, SG189, SG190, SG191, SG192, SG193, SG194, SG195, SG196, SG197, SG198, SG199, SG200, SG201, SG202, SG203, SG204, SG205, SG206, SG207, SG208, SG209, SG210, SG211, SG212, SG213, SG214, SG215, SG216, SG217, SG218, SG219, SG220, SG221, SG222, SG223, SG224, SG225, SG226, SG227, SG228, SG229, SG230, SG231, SG232, SG233, SG234, SG235, SG236, SG237, SG238, SG239, SG240, SG241, SG242, SG243, SG244, SG245, SG246, SG247, SG248, SG249, SG250, SG251, SG252, SG253, SG254, SG255, SG256, SG257, SG258, SG259, SG260, SG261, SG262, SG263, SG264, SG265, SG266, SG267, SG268, SG269, SG270, SG271, SG272, SG273, SG274, SG275, SG276, SG277, SG278, SG279, SG280, SG281, SG282, SG283, SG284, SG285, SG286, SG287, SG288, SG289, SG290, SG291, SG292, SG293, SG294, SG295, SG296, SG297, SG298, SG299, SG300, SG301, SG302, SG303, SG304, SG305, SG306, SG307, SG308, SG309, SG310, SG311, SG312, SG313, SG314, SG315, SG316, SG317, SG318, SG319, SG320, SG321, SG322, SG323, SG324, SG325, SG326, SG327, SG328, SG329, SG330, SG331, SG332, SG333, SG334, SG335, SG336, SG337, SG338, SG339, SG340, SG341, SG342, SG343, SG344, SG345, SG346, SG347, SG348, SG349, SG350, SG351, SG352, SG353, SG354, SG355, SG356, SG357, SG358, SG359, SG360, SG361, SG362, SG363, SG364, SG365, SG366, SG367, SG368, SG369, SG370, SG371, SG372, SG373, SG374, SG375, SG376, SG377, SG378, SG379, SG380, SG381, SG382, SG383, SG384, SG385, SG386, SG387, SG388, SG389, SG390, SG391, SG392, SG393, SG394, SG395, SG396, SG397, SG398, SG399, SG400, SG401, SG402, SG403, SG404, SG405, SG406, SG407, SG408, SG409, SG410, SG411, SG412, SG413, SG414, SG415, SG416, SG417, SG418, SG419, SG420, SG421, SG422, SG423, SG424, SG425, SG426, SG427, SG428, SG429, SG430, SG431, SG432, SG433, SG434, SG435, SG436, SG437, SG438, SG439, SG440, SG441, SG442, SG443, SG444, SG445, SG446, SG447, SG448, SG449, SG450, SG451, SG452, SG453, SG454, SG455, SG456, SG457, SG458, SG459, SG460, SG461, SG462, SG465, SG468, SG470, SG472, SG473, SG474, SG475, SG476, SG477, SG478, SG479, SG480, SG481, SG482, SG483, SG484, SG485, SG486, SG487, SG488, SG489, SG490, SG491, SG492, SG493, SG494, SG495, SG496, SG497, SG498, SG499, SG500, SG501, SG502, SG503, SG504, SG505, SG506, SG507, SG508, SG509, SG510, SG511, SG512, SG513, SG514, SG515, SG516, SG517, SG518, SG519, SG520, SG521, SG522, SG523, SG524, SG525, SG526, SG527, SG428, SG529, SG530, SG531, SG532, SG533, SG534, SG535, SG536, SG537, SG538, SG539, SG540, SG541, SG542, SG543, SG544, SG545, SG546, SG547, SG548, SG549, SG550, SG551, SG552, SG553, SG554, SG555, SG556, SG557, SG558, SG559, SG560, SG561, SG562, SG563. 
         [0085]    Additionally, the invention provides oligonucleotides useful to be used as controls in the method of the invention. On the one hand as integrity controls, the pairs of oligonucleotides SG463 and SG464 (complementary, respectively at ends 5′ and 3′ of the β-actin gene) and SG466 and SG467 (complementary, respectively, to ends 5′ and 3′ of the GAPD gene) are provided. Additionally, oligonucleotides SSPC1, SSPC2, SSPC3, SSPC4, SSPC5, SSPC6 and SSPC7 are provided, which may be used as exogenous internal positive controls of the process quality after adding to the sample which contains the starting mRNA molecules of polyadenylated nucleic acids which contain fragments which correspond in their sequence to those of these oligonucleotides (such as the transcripts corresponding to the genes wherefrom said nucleotides are derived) and which are subjected to the same processing as the starting mRNA, as well as oligonucleotides SCN2, SCN3, SCN6, SCN8, SCN11, SCN12 and SCN13, designed to be used as positive hybridization controls and oligonucleotides SCN1, SCN5, SCN7, SCN10, SC1, SC2, SC3, SC4, SC5, SC6 and SC7, designed to be used as negative controls; they all comply with the conditions of having low homology with human genes, in addition to complying with the same conditions of the oligonucleotides complementary to human genes of being of similar lengths and all of them having GC contents in the range of 40% to 60%, correspond to zones situated at less than 3000 nucleotides from end 3′ (poly(A)) of the non-human mRNA which would be capable of detecting and being constituted by sequences which coincide in their sense with those of the corresponding mRNA. Any composition which contains at least one of oligonucleotides SG463, SG464, SG466, SG467, SSPC1, SSPC2, SSPC3, SSPC4, SSPC5, SSPC6, SSPC7, SCN2, SCN3, SCN6, SCN8, SCN11, SCN12, SCN13, SCN1, SCN5, SCN7, SCN10, SC1, SC2, SC3, SC4, SC5, SC6 and SC7, in combination with at least one of the oligonucleotides complementary to human genes of the invention mentioned above is also a composition included in the scope of the present invention. 
         [0086]    It is especially preferred that the oligonucleotides which form part of a composition of the invention are bound to a solid support. In particular, those are preferred of said compositions wherein the distribution of the oligonucleotides on the solid support are of ordered form, whereby the solid support is a rectangular piece of glass similar to a microscope slide and that the oligonucleotides are bound to the glass by covalent bonds; the compositions which meet said characteristics are referred to in the rest of the specification with the words “microarray”, “chip” or “microchip”. Among these compositions in the form of microarray, there is a special preference for those which contain more than one copy of each one of the oligonucleotides which form part thereof, very especially preferring that the number of copies of each one of the nucleotides present is at least 12. 
         [0087]    The scope of the invention also includes any diagnostic device which comprises a composition of the invention. The expression “diagnostic device” refers not only to that which serves to determine if the individual suffers from a disease or not but also those which serve to classify the disease an individual is suffering from as belonging to a subtype associated to a determined form of future evolution of said disease and, which therefore, also have a prognostic value of the future evolution of the disease. 
         [0088]    The invention also provides a method for diagnosing a neoplasia originating from hematopoietic cells and/or making a prognosis of the evolution thereof which comprises the in vitro detection from a biological sample and the statistical analysis of the expression level of at least one significant gene for classifying the sample as associated or not to said neoplasia, a gene which is selected from the group composed of GABARAP, NPM3, ABCB1, ABCB4, ABCC3, ABCC5, ABCC6, ABHD1, ABL1, ACTN1, AF1q, AKR1A1, ALDH1A1, ALK, ANK2, ANPEP, ANXA6, ANXA7, APAF1, APEX, ARHGEF2, ARS2, ASNS, ATIC, ATM, ATP5O, BAX, BCL10, BCL2, BCL2A1, BCL2L1, BCL2LAA, BCL3, BCL6, BCL7A, BCL7b, BCR, BECN1, BIK, BIRC3, BIRC5, BLMH, BLR1, BLVRB, BMI1, BMP6, BRMS1, BST2, BTG1, BUB1, C21orf33, C5orf13, CA12, CALD1, CANP2, CASC3, CASP1, CASP3, CASP4, CASP5, CASP6, CASP7, CASP8, CASP9, CAST, CATSD, CBFA2T1, CBFB, CCNA1, CCNB1, CCND1, CCND2, CCND3, CCNE1, CCR6, CCR7, CCT6A, CD14, CD19, CD2, CD22, CD24, CD28, CD33, CD34, CD36, CD38, CD3E, CD4, CD44, CD47, CD48, CD5, CD58, CD59, CD6, CD7, CD79A, CD79B, CD8, CD81, CD83, CD86, CD9, CDA, CDC25A, CDC25B, CDK2, CDK4, CDK5R1, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CDKN3, CDW52, CEBPA, CEBPB, CEBPD, CFL1, CKMT1, CKS2, CML66, COL3A1, COL4A6, CR2, CREB1, CREBBP, CRYAB, CSF2, CSF3, CSRP2, CTGF, CTSB, CUZD1, CXADR, CXCL9, CXCR3, CXCR4, CYC1, CYP1A1, CYP2A6, DAD-1, DAPK1, DCK, DDX6, DEK, DHFR, DLAD, DNAJA1, DNMT3B, DNTT, DOK1, DPF2, DPP4, DRG1, DRP2, E2F1, EB-1, EBI2, EDF1, EEF1A1, EEF1B2, EEF1D, EEF1G, EFNB1, EGFR, EGR1, EIF2B2, EIF3S2, EIF4B, EIF4E, EIF5A, ELF1, ELF4, ENPP1, EphA3, EPOR, ERBB2, ERBB4, ERCC1, ERCC2, ERCC3, ERCC5, ERCC6, ETS1, ETS2, ETV6, ETV7, EZH2, FABP5, FADD, FAIM3, FAM38A, FARP1, FAT, FCER2, FCGR3A, FCGR3B, FGFR1, FGFR3, FGR, FHIT, FKBP9, FLI1, FLJ22169, FLT3, FN1, FNTB, FOS, FUS, G1P2, GABPB2, GATA1, GATA2, GATA3, GCET2, GDI2, GGA3, GJA1, GLUD1, GNL3, GOT1, GRB2, GRIA3, GRK4, GSTP1, GSTT1, GUSB, GZMA, H2AFX, H3F3A, HCK, HELLS, HIF1A, HIST1H2BN, HLA-A, HLA-DPA1, HLA-DQA1, HLA-DRA, HLA-DRB3, HLF, HMMR, HNRPH3, HNRPL, HOXA10, HOXA9, HOXD8, HOXD9, HRAS, HSD17B1, HSPB1, IBSP, ICAM1, ICAM3, ID2, IER3, IFRD1, IGFBP2, IGFBP3, IGFIR, IGLV6-57, IL10, IL15, IL1B, IL2, IL2RA, IL3, IL32, IL3RA, IL4R, IL6, IL6R, IL8, ILF2, IRF1, IRF2, IRF4, IRF8, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGAL, ITGAM, ITGAX, ITGB1, ITGB2, JAK1, JAK2, JUNB, KAI1, KIAA0247, KIAA0864, KIT, KLF1, KLF13, KRAS2, KRT18, LADH, LAG3, LASP1, LCK, LCP1, LEPR, LGALS3, LGALS7, LIF, LIMS1, LMO2, LOC285148, LRP, LSP1, LYL1, LYN, LYZ, MAFB, MAFK, MAGEA1, MAL, MAP3K12, MAP4K1, MAPK10, MAZ, MBP1, MCL1, MCM3, MCM7, MDM2, MEIS1, MEN1, MERTK, MKI67, MLF1, MLF2, MLL, MLLT10, MME, MMP2, MMP7, MMP8, MMP9, MNDA, MPL, MPO, MRPL37, MS4A1, MTCP1, MUC-1, MX1, MYB, MYBL1, MYC, MYOD1, NCALD, NCAM1, NCL, NDP52, NDRG1, NDUFA1, NDUFB, NF1, NFATC1, NFIC, NFKB1, NFIB1A, NINJ1, NPM1, NR3C1, NUMA1, NXF1, ODC1, OGGI, OLIG2, OPRD1, p14ARF, P55CDC, PABPC1, PAX5, PAX6, PAX8, PBX1, PBX3, PCA1, PCD, PCNA, PDCD1, PDGFA, PDGFRB, PDHA1, PGF, PGRMC1, PICALM, PLA2G6, PLAU, PLK1, PLP, PLS3, PLZF, PML, PMM1, POLR2c, POU2F2, PPP1CC, PRAME, PRKCI, PRKCQ, PRKDC, PRL, PRTN3, PSMA5, PSMB4, PSMC5, PSMD7, PTEN, PTGS1, PTHLH, PTK2, PTK2B, PTN, PTPRCCD, PYGB, RAD51, RAF1, RAG1, RARA, RARB, RB1, RBBP4, RBBP6, RBBP8, RBP4, RET, RGS1, RGS1, RIS1, RORA, RPL17, RPL23A, RPL24, RPL36A, RPL37A, RPL41, RPS3, RPS5, RPS9, RUNX1, RxRA, S100A2, S100A8, SDC1, SDHD, SELE, SELL, SEPW1, SERPINA9, SERPINB5, SERPNINA9, SFTPB, SIAT4A, SLC7A5, SNRPB, SOSTDC1, SP1, SPI1, SPN, SPRRIA, SREBF1, SSBP1, STAT1, STAT3, STAT5B, SUMO1, TACSTD2, TAGLN2, TAL1, TBP, TCEB1, TCF1, TCF3, TCF7, TCL1A, TCRbeta, TEGT, TERF1, TERT, TFCP2, TFRC, THBS1, THPO, TIA-2, TIAM1, TK1, TLX1, TMEM4, TNF, TNFRSF10C, TNFRSF1A, TNFRSF25, TNFRSF5, TNFRSF6, TNFRSF8, TNFSF10, TNFSF5, TNFSF6, TOP2A, TOPORS, TP73, TRA@, TRADD, TRAF3, TRAP1, TRIB2, TXNRD1, UBE2C, UHRF1, UVRAG, VCAM1, VEGF, VPREB1, WBSCR20C, WNT16, WTI, XBP1, XPO6, XRCC3, XRCC5, ZAP70, ZFPL1, ZNF42, ZNFN1A1, ZYX, 18S rRNA, 28S rRNA, and whose expression level is determined by the evaluation of the concentration of its corresponding mRNA by the use of at least one probe which has a sequence complementary to a fragment of a strand of said gene, a probe which is selected from the group of oligonucleotides composed of: SG1, SG2, SG3, SG4, SG5, SG6, SG7, SG8, SG9, SG10, SG11, SG12, SG13, SG14, SG15, SG16, SG17, SG18, SG19, SG20, SG21, SG22, SG23, SG24, SG25, SG26, SG27, SG28, SG29, SG30, SG31, SG32, SG33, SG34, SG35, SG36, SG37, SG38, SG39, SG40, SG41, SG42, SG43, SG44, SG45, SG46, SG47, SG48, SG49, SG50, SG51, SG52, SG53, SG54, SG55, SG56, SG57, SG58, SG59, SG60, SG61, SG62, SG63, SG64, SG65, SG66, SG67, SG68, SG69, SG70, SG71, SG72, SG73, SG74, SG75, SG76, SG77, SG78, SG79, SG80, SG81, SG82, SG83, SG84, SG85, SG86, SG87, SG88, SG89, SG90, SG91, SG92, SG93, SG94, SG95, SG96, SG97, SG98, SG99, SG100, SG101, SG102, SG103, SG104, SG105, SG106, SG107, SG108, SG109, SG110, SG111, SG112, SG113, SG114, SG115, SG116, SG117, SG118, SG119, SG120, SG121, SG122, SG123, SG124, SG125, SG126, SG127, SG128, SG129, SG130, SG131, SG132, SG133, SG134, SG135, SG136, SG137, SG138, SG139, SG140, SG141, SG142, SG143, SG144, SG145, SG146, SG147, SG148, SG149, SG150, SG151, SG152, SG153, SG154, SG155, SG156, SG157, SG158, SG159, SG160, SG161, SG162, SG163, SG164, SG165, SG166, SG167, SG168, SG169, SG170, SG171, SG172, SG173, SG174, SG175, SG176, SG177, SG178, SG179, SG180, SG181, SG182, SG183, SG184, SG185, SG186, SG187, SG188, SG189, SG190, SG191, SG192, SG193, SG194, SG195, SG196, SG197, SG198, SG199, SG200, SG201, SG202, SG203, SG204, SG205, SG206, SG207, SG208, SG209, SG210, SG211, SG212, SG213, SG214, SG215, SG216, SG217, SG218, SG219, SG220, SG221, SG222, SG223, SG224, SG225, SG226, SG227, SG228, SG229, SG230, SG231, SG232, SG233, SG234, SG235, SG236, SG237, SG238, SG239, SG240, SG241, SG242, SG243, SG244, SG245, SG246, SG247, SG248, SG249, SG250, SG251, SG252, SG253, SG254, SG255, SG256, SG257, SG258, SG259, SG260, SG261, SG262, SG263, SG264, SG265, SG266, SG267, SG268, SG269, SG270, SG271, SG272, SG273, SG274, SG275, SG276, SG277, SG278, SG279, SG280, SG281, SG282, SG283, SG284, SG285, SG286, SG287, SG288, SG289, SG290, SG291, SG292, SG293, SG294, SG295, SG296, SG297, SG298, SG299, SG300, SG301, SG302, SG303, SG304, SG305, SG306, SG307, SG308, SG309, SG310, SG311, SG312, SG313, SG314, SG315, SG316, SG317, SG318, SG319, SG320, SG321, SG322, SG323, SG324, SG325, SG326, SG327, SG328, SG329, SG330, SG331, SG332, SG333, SG334, SG335, SG336, SG337, SG338, SG339, SG340, SG341, SG342, SG343, SG344, SG345, SG346, SG347, SG348, SG349, SG350, SG351, SG352, SG353, SG354, SG355, SG356, SG357, SG358, SG359, SG360, SG361, SG362, SG363, SG364, SG365, SG366, SG367, SG368, SG369, SG370, SG371, SG372, SG373, SG374, SG375, SG376, SG377, SG378, SG379, SG380, SG381, SG382, SG383, SG384, SG385, SG386, SG387, SG388, SG389, SG390, SG391, SG392, SG393, SG394, SG395, SG396, SG397, SG398, SG399, SG400, SG401, SG402, SG403, SG404, SG405, SG406, SG407, SG408, SG409, SG410, SG411, SG412, SG413, SG414, SG415, SG416, SG417, SG418, SG419, SG420, SG421, SG422, SG423, SG424, SG425, SG426, SG427, SG428, SG429, SG430, SG431, SG432, SG433, SG434, SG435, SG436, SG437, SG438, SG439, SG440, SG441, SG442, SG443, SG444, SG445, SG446, SG447, SG448, SG449, SG450, SG451, SG452, SG453, SG454, SG455, SG456, SG457, SG458, SG459, SG460, SG461, SG462, SG465, SG468, SG469, SG470, SG471, SG472, SG473, SG474, SG475, SG476, SG477, SG478, SG479, SG480, SG481, SG482, SG483, SG484, SG485, SG486, SG487, SG488, SG489, SG490, SG491, SG492, SG493, SG494, SG495, SG496, SG497, SG498, SG499, SG500, SG501, SG502, SG503, SG504, SG505, SG506, SG507, SG508, SG509, SG510, SG511, SG512, SG513, SG514, SG515, SG516, SG517, SG518, SG519, SG520, SG521, SG522, SG523, SG524, SG525, SG526, SG527, SG428, SG529, SG530, SG531, SG532, SG533, SG534, SG535, SG536, SG537, SG538, SG539, SG540, SG541, SG542, SG543, SG544, SG545, SG546, SG547, SG548, SG549, SG550, SG551, SG552, SG553, SG554, SG555, SG556, SG557, SG558, SG559, SG560, SG561, SG562, SG563. 
         [0089]    The genes which form part of the aforementioned group are human genes. Therefore, whenever the words “subject” or “individual” are used hereinafter, they will make reference to a human being. 
         [0090]    A particular case of this method is that which comprises an additional previous step of identification of genes significant for the classification of the biological sample analysed as associated or not to a specific type of neoplasia originating from hematopoietic cells, a classification which includes not only the diagnosis of the existence of said neoplasia in the individual from which the sample has been taken, but which may also consist, in additional or alternative form, of the discrimination between specific subtypes of said neoplasia which correspond to different future forms of evolution of said neoplasia this constituting the classification of one or another subtype of the evolution of the neoplasia considered in the future. In this particular case of the method of the invention which comprises a previous step of identification of genes significant for making the desired classification, said previous step comprises the steps of:
       a) deciding the possible categories wherein the sample can be classified;   b) obtaining biological samples from individuals which have previously been assigned by a method different to that claimed to any of the possible classification categories, so that there are samples of each one of the possible categories;   c) obtaining the total mRNA of each one of the samples;   d) obtaining the corresponding total cRNA, labelled by a method which allows its subsequent detection, of at least one aliquot of each one of the samples of mRNA, an aliquot whereto is added before the obtainment of the cRNA at least one sequence of polyadenylated nucleotides of low homology with human genes for which it acts as internal positive control of the process;   e) adding to one of the aliquots of cRNA which are going to be used in step f) at least one oligonucleotide of low homology with human genes different from and not complementary to any possible sequence of nucleotides which have been added in step d), for which it acts as positive hybridization control;   f) hybridizing, in strict conditions, at least one aliquot of total cRNA of each one of the samples with at least one microarray which comprises at least two copies of each one of the oligonucleotides from the group composed of:
 
SG1, SG2, SG3, SG4, SG5, SG6, SG7, SG8, SG9, SG10, SG11, SG12, SG13, SG14, SG15, SG16, SG17, SG18, SG19, SG20, SG21, SG22, SG23, SG24, SG25, SG26, SG27, SG28, SG29, SG30, SG31, SG32, SG33, SG34, SG35, SG36, SG37, SG38, SG39, SG40, SG41, SG42, SG43, SG44, SG45, SG46, SG47, SG48, SG49, SG50, SG51, SG52, SG53, SG54, SG55, SG56, SG57, SG58, SG59, SG60, SG61, SG62, SG63, SG64, SG65, SG66, SG67, SG68, SG69, SG70, SG71, SG72, SG73, SG74, SG75, SG76, SG77, SG78, SG79, SG80, SG81, SG82, SG83, SG84, SG85, SG86, SG87, SG88, SG89, SG90, SG91, SG92, SG93, SG94, SG95, SG96, SG97, SG98, SG99, SG100, SG101, SG102, SG103, SG104, SG105, SG106, SG107, SG108, SG109, SG110, SG111, SG112, SG113, SG114, SG115, SG116, SG117, SG118, SG119, SG120, SG121, SG122, SG123, SG124, SG125, SG126, SG127, SG128, SG129, SG130, SG131, SG132, SG133, SG134, SG135, SG136, SG137, SG138, SG139, SG140, SG141, SG142, SG143, SG144, SG145, SG146, SG147, SG148, SG149, SG150, SG151, SG152, SG153, SG154, SG155, SG156, SG157, SG158, SG159, SG160, SG161, SG162, SG163, SG164, SG165, SG166, SG167, SG168, SG169, SG170, SG171, SG172, SG173, SG174, SG175, SG176, SG177, SG178, SG179, SG180, SG181, SG182, SG183, SG184, SG185, SG186, SG187, SG188, SG189, SG190, SG191, SG192, SG193, SG194, SG195, SG196, SG197, SG198, SG199, SG200, SG201, SG202, SG203, SG204, SG205, SG206, SG207, SG208, SG209, SG210, SG211, SG212, SG213, SG214, SG215, SG216, SG217, SG218, SG219, SG220, SG221, SG222, SG223, SG224, SG225, SG226, SG227, SG228, SG229, SG230, SG231, SG232, SG233, SG234, SG235, SG236, SG237, SG238, SG239, SG240, SG241, SG242, SG243, SG244, SG245, SG246, SG247, SG248, SG249, SG250, SG251, SG252, SG253, SG254, SG255, SG256, SG257, SG258, SG259, SG260, SG261, SG262, SG263, SG264, SG265, SG266, SG267, SG268, SG269, SG270, SG271, SG272, SG273, SG274, SG275, SG276, SG277, SG278, SG279, SG280, SG281, SG282, SG283, SG284, SG285, SG286, SG287, SG288, SG289, SG290, SG291, SG292, SG293, SG294, SG295, SG296, SG297, SG298, SG299, SG300, SG301, SG302, SG303, SG304, SG305, SG306, SG307, SG308, SG309, SG310, SG311, SG312, SG313, SG314, SG315, SG316, SG317, SG318, SG319, SG320, SG321, SG322, SG323, SG324, SG325, SG326, SG327, SG328, SG329, SG330, SG331, SG332, SG333, SG334, SG335, SG336, SG337, SG338, SG339, SG340, SG341, SG342, SG343, SG344, SG345, SG346, SG347, SG348, SG349, SG350, SG351, SG352, SG353, SG354, SG355, SG356, SG357, SG358, SG359, SG360, SG361, SG362, SG363, SG364, SG365, SG366, SG367, SG368, SG369, SG370, SG371, SG372, SG373, SG374, SG375, SG376, SG377, SG378, SG379, SG380, SG381, SG382, SG383, SG384, SG385, SG386, SG387, SG388, SG389, SG390, SG391, SG392, SG393, SG394, SG395, SG396, SG397, SG398, SG399, SG400, SG401, SG402, SG403, SG404, SG405, SG406, SG407, SG408, SG409, SG410, SG411, SG412, SG413, SG414, SG415, SG416, SG417, SG418, SG419, SG420, SG421, SG422, SG423, SG424, SG425, SG426, SG427, SG428, SG429, SG430, SG431, SG432, SG433, SG434, SG435, SG436, SG437, SG438, SG439, SG440, SG441, SG442, SG443, SG444, SG445, SG446, SG447, SG448, SG449, SG450, SG451, SG452, SG453, SG454, SG455, SG456, SG457, SG458, SG459, SG460, SG461, SG462, SG465, SG468, SG469, SG470, SG471, SG472, SG473, SG474, SG475, SG476, SG477, SG478, SG479, SG480, SG481, SG482, SG483, SG484, SG485, SG486, SG487, SG488, SG489, SG490, SG491, SG492, SG493, SG494, SG495, SG496, SG497, SG498, SG499, SG500, SG501, SG502, SG503, SG504, SG505, SG506, SG507, SG508, SG509, SG510, SG511, SG512, SG513, SG514, SG515, SG516, SG517, SG518, SG519, SG520, SG521, SG522, SG523, SG524, SG525, SG526, SG527, SG428, SG529, SG530, SG531, SG532, SG533, SG534, SG535, SG536, SG537, SG538, SG539, SG540, SG541, SG542, SG543, SG544, SG545, SG546, SG547, SG548, SG549, SG550, SG551, SG552, SG553, SG554, SG555, SG556, SG557, SG558, SG559, SG560, SG561, SG562, SG563,
 
a microarray which additionally comprises:
   a. at least two points which correspond to different aliquots of the solvent wherein nucleotides are found at the time of their deposit on the surface of the microarray, for which they serve as blank,   b. at least two copies of at least one oligonucleotide for each one of the polyadenylated sequences added in step d), an oligonucleotide whose sequence will correspond to a fragment, different from the polyadenylation zone, of the sequence of polyadenylated nucleotides whose evolution in the process has to be controlled;   c. for each one of the oligonucleotides added in step e), at least two copies of an oligonucleotide complementary thereto;   d. at least two copies of each member of at least one pair of oligonucleotides wherein the sequence of one of the members corresponds to a sequence of zone 5′ and the sequence of the other corresponds to a sequence of zone 3′ of the mRNA of a gene which is expressed in constitutive form in any cell of hematopoietic origin;   e. at least two copies of at least one oligonucleotide of low homology with human genes different from any of the oligonucleotides defined in section b. and different from any of the synthetic oligonucleotides added optionally in step e);   g) detecting and quantifying the signal of cRNA hybridized with each one of the copies of each one of the oligonucleotides present in the microarray, as well as the signal corresponding to the points of the solvent;   h) calculating the average level of intensity of hybridization of each one of the oligonucleotides of the microarray calculating the average of the intensities of the copies of each one of the oligonucleotides;   i) taking the hybridization as valid if the following conditions are complied with:
           a. the ratio between the average intensity and the average background of all the oligonucleotides of the microarray is greater than 10;   b. the value of the average coefficient of variation of all the replicas of oligonucleotides should be less than 0.3;   c. the average value of negative control should be less than 2.5 times the average value of the points corresponding to the solvent;   d. there is a signal both in the hybridization controls and in the internal positive controls used as process control;   
           j) normalizing the data;   k) eliminating the oligonucleotides with values of average intensity minus average background noise less than approximately 2 times the average value obtained with the points corresponding to the solvent, as well as the oligonucleotides with an interquartile range of normalized intensity throughout the samples less than 0.3;   l) performing the statistical analysis to find the statistically significant oligonucleotides to differentiate between the different categories and be able to classify a sample which has not been previously assigned to any category, choosing said oligonucleotides among those which have not been eliminated in the previous steps, until obtaining “n” oligonucleotides which either have a value of p less than a limit which is chosen from the open range of 0 to 0.05, preferably using for it a method with capacity to reduce false positives, or that which best defines the category established;   m) checking that the grouping of the samples according to the differences in intensities between the different samples detected for the statistically significant oligonucleotides gives rise to the samples being classified in the same categories as those which had previously been assigned by a different method.       
 
         [0113]    It is preferred that the average value calculated in section h) is the trimmed mean, for which reason it is preferable that the microarray comprises at least four copies of each one of the oligonucleotides present therein. 
         [0114]    The normalization can be carried out with different methods. There is preference for the use of functions contained in access packages freely accessed over the Internet designed for the processing, calculation and graphic representation of data, such as the packages designed in R programming language, available to download from CRAN (http://cran.r-project.org/) or Bioconductor (http://www.bioconductor.orq). The “variance stabilization normalization” method available in the “vsn” package in R. 
         [0115]    The identification of the statistically significant oligonucleotides to differentiate between the different categories can be carried out using different methods, having preference for those wherein a value p is determined that determines the threshold of probability under which all the genes whose expression difference has a value less than p would be considered significant and, among these, those which have the capacity to carry out corrections on the value of p, such as, among others, Bonferroni&#39;s method or Welch&#39;s test. The value of p will be chosen from the open range of 0 to 0.05, preferring, when possible, a value of p close to 0.001 and with correction, it being possible to increase said value at maximum to 0.05 (value which is not included among those possible) until which statistically significant oligonucleotides are found to differentiate between the categories among which one wants to classify the samples. A possibility for carrying out these calculations is, again, the use of functions contained in packages freely accessed over the Internet designed for the processing, calculation and graphic representation of data. In particular, the mt.maxT function of the multtest package in R can be used for the identification of the statistically significant oligonucleotides. 
         [0116]    Another possibility for the identification of statistically significant oligonucleotides to be able to differentiate between the categories of established samples is the use of the “nearest shrunken centroids” method, a variation of the “nearest centroids” method (Tibshirani et al., 2002), which identifies a group of genes which best characterizes a predefined class and uses this group of genes to predict the class which new samples belong to. To do this, again functions contained in packages freely accessed over the internet may be resorted to, such as the “pam a ” package in R, wherein it is possible to find functions to carry out the so-called “Prediction Analysis for Microarrays (PAM)”, which makes use of the “nearest shrunken centroids” method. 
         [0117]    After identifying the statistically significant genes to distinguish between categories of samples established from the corresponding oligonucleotides, they can be used for classifying new samples due to similarity between the expression profile of those genes in the sample analysed and those corresponding to each one of the classification categories. Alternatively, when there are only 2 possible classification categories (which will be normal when one wants to diagnose the presence or absence of a certain type of leukaemia in an individual), it is possible to obtain a mathematical function of classification of samples which determine the probability “p i ” of a sample “i” belonging to one category or another. To do this, a subunit of the samples is chosen which have been previously assigned to each one of the possible categories by a method different to that of the invention and the value of 0 is arbitrarily associated to each one of the samples of one of the categories “a” (typically, the category of “not” associated to the leukemia one wants to diagnose”) of belonging to the other possible category, whilst each one of the samples of the subunit belonging to the other possible category “b” (typically, the category of “associated” to the leukemia one wants to diagnose”) arbitrarily receives the value “1” for its probability of belonging to its own category. With this, logistical regression is used to calculate, with the aid of the probability values assigned to each one of the samples and the values of normalized trimmed mean intensity obtained for each one of the samples with each one of the “n” oligonucleotides which has been identified as a statistically significant oligonucleotide in the previous step, coefficients for each one of said oligonucleotides which make it possible to obtain a function of probability p i  of a sample “i” belonging to category “b”, a function which will be of the type 
         [0000]        p   i =1/(1+ e   −xi ) 
         [0000]    and which results from the algebraic transformation of the expression which equals Neperian logarithm of the quotient between the probability of an event occurring and the probability that it does not occur at a function x i  which includes as variables each one of the factors which may influence the event, i.e. 
         [0000]    
       
         
           
             
               ln 
                
               
                 p 
                 
                   1 
                   - 
                   p 
                 
               
             
             = 
             
               x 
               i 
             
           
         
       
     
         [0000]    function x i  which, in the present case, will depend on the intensity values obtained for each one of the statistically significant oligonucleotides and which responds to an expression of the type: 
         [0000]    
       
         
           
             
               x 
               i 
             
             = 
             
               constant 
               + 
               
                 
                   ∑ 
                   
                     m 
                     = 
                     1 
                   
                   n 
                 
                  
                 
                   ( 
                   
                     
                       coeff_olig 
                       m 
                     
                     * 
                     
                       lmn 
                       i 
                     
                      
                     
                       _olig 
                       m 
                     
                   
                   ) 
                 
               
             
           
         
       
     
         [0000]    where
       coeff_olig m  represents the coefficient calculated for a specific oligonucleotide “m”   Imn i     —   olig m  represents the average value of normalized intensity obtained in the hybridization of the sample i calculated for the oligonucleotide “m”   “m” varies from 1 to “n”   n is the total number of oligonucleotides considered significant.       
 
         [0122]    The function p i  obtained after calculating by logistical regression the coefficient corresponding to each oligonucleotide permits classifying a sample “i” as belonging to one or another category, considering that the values of p i  over 0.5 (and which will be less than or equal to 0) indicate that the sample belongs to category “b”, whilst the values of p i  less than 0.5 indicate that the sample belongs to category “a”. Said function p i  will be considered valid if, on being applied to the samples wherefrom it has been deduced, it is capable of classifying them correctly and, furthermore, as it is applied to the subgroup of samples which have not been taken into account to deduce the function, but whose category is known as it has been previously assigned by a method other than that of the invention, it is also capable of classifying them correctly. 
         [0123]    Alternatively, when the identification of the statistically significant genes has been performed using the “Prediction Analysis for Microarrays” method, the classifier can be obtained with the corresponding functions of the “pamr a ” package in R, which also starts from the assignment of the value of probability 0 to a subgroup of members of one of the categories and the value of probability 1 to a subgroup of the members of the other category. Again, the calculation of coefficients for statistically significant oligonucleotides permits the calculation of values of probability of belonging to one or another category, also considering that the values over 0.5 indicate belonging to the category whose members are arbitrarily assigned value 1 and the values less than 0.5 indicate belonging to the other category. 
         [0124]    A particular case of the method of the invention is that wherein one wants to classify samples as associated or not to a type of leukemia. In that case, blood samples are preferred, especially those of peripheral blood, as biological samples to carry out in vitro the method of the invention. 
         [0125]    Once the statistically significant genes have been identified to associate a determined type of neoplasia as originating from hematopoietic cells, the method of the invention can be used for classifying samples according to the expression level of said genes in said samples. The neoplasia can be, for example, a specific type of leukemia. A particular case of this embodiment of the method of the invention is constituted by the association of chronic lymphatic leukemia, thus allowing the diagnosis of this disease by the method of the invention. To do this, significant genes are considered to be those genes whose expression level is analysed on applying the method of the invention at least those of the group of CD79A, FAIM3, HLA-DRA, HLA-DRB3, HLA-DQA1 and the analysis is carried out on blood samples. The method can be additionally applied including the analysis of the expression level of at least genes IRF8 and COL3A1. Preferably, the analysis of the expression level of these genes is carried out by evaluating the level of their corresponding mRNA by hybridization of their corresponding cRNA with oligonucleotides SG117, SG428, SG459, SG507, SG508, SG461 and SG493, which are preferred to be associated to a solid support forming part of a microarray. When the evaluation of the hybridized cRNA with each one of those oligonucleotides is carried out thanks to the prior labelling of the cRNA with biotin, the staining of the microarray hybridized with streptavidin conjugated with a fluorophore and the detection of the signal emitted by said fluorophore, it is preferred that the fluorophore is Cy3, which permits diagnosing the presence of CLL in the subject from which the sample has been taken by the classification of sample “i” analysed as associated to CLL from the calculation of the probability that said sample is associated to CLL from the formula p i =1/(1+e −x     i   ), wherein x i  is calculated by the formula 
         [0000]        x   i =−719.241486+(2.44756372* Imn   i     —     CD 79 A )+(7.38657611* Imn   i     —     FAIM 3)+(23.1465464* Imn   i     —     HLA - DRA )+(43.6287742* Imn   i     —     IRF 8)−(19.3978182* Imn   i     —     COL 3A1)−(2.80282646* Imn   i     —     HLA - DRB 3)+(49.5345672 *Imn   i     —     HLA - DQA 1)
       formula wherein each one of the values denominated with the abbreviation “Imn i ” followed by the abbreviation of a gene makes reference to the average value of normalized intensity obtained after detecting the hybridization signal corresponding to the oligonucleotide which is being used as probe to evaluate the expression of the said gene
 
and which permits classifying the subject as subject not suffering from CLL if the value of p i  is less than 0.5 and as subject suffering from CLL if the value of p i  is greater than 0.5.
 
Alternatively, significant genes can be considered as those whose expression level is analysed on applying the method of the invention for the diagnosis of CLL at least those of the group of CD79A, FAIM3, HLA-DRA, HLA-DRB3, HLA-DQA1, additionally including the analysis of the expression level of at least gene CDW52. Preferably, the analysis of the expression level of these genes is carried out by evaluating the level of its corresponding mRNA by hybridization of its corresponding cRNA with oligonucleotides SG117, SG428, SG459, SG507, SG508 and SG237, which it is preferred are associated to a solid support forming part of a microarray.
       
 
         [0127]    Another particular case of the application of the method of the invention for classifying samples as associated to a specific type of leukemia according to the expression level in said samples of statistically significant genes constitutes the classification of a sample as associated to a specific subtype of chronic lymphatic leukemia, “stable” CLL or “progressive” CLL, which makes it possible that the method of the invention serves to make a prognosis for the future evolution of subjects which have been diagnosed with CLL. When the samples analysed are of peripheral blood, the genes considered statistically significant to perform the classification of the samples are at least genes PSMB4, FCER2 and POU2F2, it being possible to additionally analyse the expression level of at least one gene selecting the group composed of ODC1, CD79A, CD2, CD3E, CD5, MS4A1, EIF4E, FHIT, NR3C1, LCP1, MAPK10, ABCC5, XRCC3, CML66, PLZF, RBP4 or the totality thereof. 
         [0128]    An additional aspect of the invention is the use of devices to evaluate the expression level of at least one of the genes of the group composed of PSMB4, FCER2, POU2F2, ODC1, CD79A, CD2, CD3E, CD5, MS4A1, EIF4E, FHIT, NR3C1, LCP1, MAPK10, ABCC5, XRCC3, CML66, PLZF, RBP4, CD79A, FAIM3, HLA-DRA, HLA-DRB3, HLA-DQA1, IRF8 and COL3A1 with the aim of diagnosing the presence of CLL in an individual and/or making a prognosis of his/her evolution. A particular case of this aspect of the invention is the use of devices of evaluation of the expression level of at least one gene of the group composed of CD79A, FAIM3, HLA-DRA, HLA-DRB3, HLA-DQA1, IRF8 and COL3A1 for the diagnosis of the presence of CLL in an individual, wherein it is preferred that the device evaluates at least the expression level of genes CD79A, FAIM3, HLA-DRA, HLA-DRB3, HLA-DQA1, it being possible for the device to evaluate, additionally, the expression level of at least genes IRF8 and COL3A1 or at least gene CDW52. Another particular case of this aspect of the invention is the use of devices of evaluation of the expression level of at least one gene of the group composed of PSMB4, FCER2, POU2F2, ODC1, CD79A, CD2, CD3E, CD5, MS4A1, EIF4E, FHIT, NR3C1, LCP1, MAPK10, ABCC5, XRCC3, CML66, PLZF, RBP4, CD79A, FAIM3, HLA-DRA, HLA-DRB3, HLA-DQA1, IRF8 and COL3A1 to make a prognosis of the future evolution of CLL in an individual. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Design of the Microarray Device 
     Genes Included in the Microarray 
       [0129]    A revision was performed of the scientific literature and genes were selected due to their special involvement in the biology of blood cells or in the pathology of the different neoplasias The genes selected can be included within these 4 large groups: 
       a) With an Important Role in the Biology of the Hematopoietic Cells: 
       [0000]    
       
         
           
             Genes whose protein is expressed or repressed in the different steps through which these cells pass in their differentiation to mature forms. 
             Genes whose protein is specifically expressed in accordance with the line whereto the cell belongs. 
             Genes which code adhesion molecules 
           
         
       
     
       b) Involved in Different Types of Hematological Neoplasias: 
       [0000]    
       
         
           
             Genes whose expression (a level of mRNA or protein) is altered in different types of neoplasias, or associated to resistance to chemotherapy 
           
         
       
     
       c) Cancer-Related: 
       [0000]    
       
         
           
             Genes which code proteins associated with proliferation, metastasis or genes whose expression is increased in a large number of tumours. 
           
         
       
     
       d) Described in Publications Related to Neoplasias: 
       [0000]    
       
         
           
             Genes which, without having a special ratio with hematological neoplasias or blood cell biology, have appeared in the scientific literature as statistically associated to a type of neoplasia 
           
         
       
     
         [0136]    The characteristics of the genes can be consulted, for example, in: www.ncbi.nlm.nih.qov/Genbank, selecting the “Gene” option in the drop-down menu which appears and entering the corresponding identification number (GenID) in the GenBank. The genes whose expression can be analysed with the microarray, their corresponding identification number in the GenBank, as well as the oligonucleotides present in the microarray to be used as probes to analyse the expression of said genes appear below in Table 1. 
         [0000]    Probes of Oligonucleotides which Represent Each Gene. 
         [0137]    For each one of the 534 genes related to hematological neoplasias, as well as for the genes corresponding to β-actin, glyceraldehyde-3-phosphate dehydrogenase, 18S rRNA and 28S rRNA, the mrRNA sequence is sought in GenBank (www.ncbi.hlm.nih.gov/Genbank/). An oligonucleotide is designed (probe) from the GenBank sequence, specific for each one of the genes selected. In some genes several oligonucleotides were designed situated in zones 5′ and 3′ of the gene, in order to analyse the integrity of the mRNA. 
         [0138]    To ensure specificity in the design of the probes, the following criteria were taken into consideration:
       Length of the probe to guarantee that all the probes are going to have a similar behaviour,   GC content of the probe between 40 and 60%. This characteristic is also taken into consideration to ensure that all the probes are going to have a similar behaviour.   Localization in the gene. Probes localized at least 3000 nucleotides from 3′ (poly(A)) of the selected mRNA sequence were localized.   Sense of the probe. A strand was chosen with “sense”, i.e. the sequences of the oligonucleotides coincide with sequences of fragments of the corresponding mRNA, instead of being sequences complementary to said fragments. This decision involves that the labelled genetic material has to be antisense (complementary to sense).   Specificity of the probe. To avoid non-specific hybridization, probes were selected which have a percentage of homology, calculated by the BLAST tool (available on the website http://www.ncbi.nlm.nih.gov/), less than 70%.       
 
         [0144]    The data on the oligonucleotides used as probes, the identification number of its corresponding sequence in the attached list, as well as data (identification number in GenBank, usual abbreviation and name) of the genes for the detection of whose expression said oligonucleotides have been designed, are shown below in the Table 1. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 Oligonucleotides used as probes to detect the expression of human genes 
               
             
          
           
               
                 Oligo- 
                   
                   
                 Usual 
                   
               
               
                 nucleotide 
                 SEQ ID NO: 
                 GenID 
                 abbreviation 
                 Description 
               
               
                   
               
             
          
           
               
                 SG1 
                 SEQ ID 
                 11337 
                 GABARAP 
                 Protein associated to the GABA receptor 
               
               
                   
                 NO: 1 
               
               
                 SG2 
                 SEQ ID 
                 28778 
                 IGLV6-57 
                 Variable lambda immunoglobulin 6-57 
               
               
                   
                 NO: 2 
               
               
                 SG3 
                 SEQ ID 
                 5092 
                 PCD 
                 6-pyruvoyl-tetrahydropterine 
               
               
                   
                 NO: 3 
                   
                   
                 synthase/dimerization cofactor of the 
               
               
                   
                   
                   
                   
                 nuclear factor of 1 alpha hepatocytes 
               
               
                   
                   
                   
                   
                 (TCF1) 
               
               
                 SG4 
                 SEQ ID 
                 83988 
                 NCALD 
                 delta neurocalcin 
               
               
                   
                 NO: 4 
               
               
                 SG5 
                 SEQ ID 
                 58511 
                 DLAD 
                 deoxyribonuclease II beta 
               
               
                   
                 NO: 5 
               
               
                 SG6 
                 SEQ ID 
                 25928 
                 SOSTDC1 
                 which contains a sclerostin 1 domain 
               
               
                   
                 NO: 6 
               
               
                 SG7 
                 SEQ ID 
                 10630 
                 TIA-2 
                 glycoprotein associated to the lung cell 
               
               
                   
                 NO: 7 
                   
                   
                 membrane, type I 
               
               
                 SG8 
                 SEQ ID 
                 5834 
                 PYGB 
                 phosphorylase, glycogen; brain 
               
               
                   
                 NO: 8 
               
               
                 SG9 
                 SEQ ID 
                 3987 
                 LIMS1 
                 with domains LIM and similar to the antigen 
               
               
                   
                 NO: 9 
                   
                   
                 of senescent cells 1 
               
               
                 SG10 
                 SEQ ID 
                 25 
                 ABL1 
                 homologue to the viral oncogene of Abelson 
               
               
                   
                 NO: 10 
                   
                   
                 v-abl 1 murine leukemia 
               
               
                 SG11 
                 SEQ ID 
                 4733 
                 DRG1 
                 GTP-binding protein regulated by 
               
               
                   
                 NO: 11 
                   
                   
                 development 1 
               
               
                 SG12 
                 SEQ ID 
                 25855 
                 BRMS1 
                 Metastasis suppressor of breast cancer 1 
               
               
                   
                 NO: 12 
               
               
                 SG13 
                 SEQ ID 
                 84696 
                 ABHD1 
                 which contains an abhydrolase 1 domain 
               
               
                   
                 NO: 13 
               
               
                 SG14 
                 SEQ ID 
                 3475 
                 IFRD1 
                 Development regulator related to interferon 1 
               
               
                   
                 NO: 14 
               
               
                 SG15 
                 SEQ ID 
                 6173 
                 RPL36A 
                 Ribosomal protein L36a 
               
               
                   
                 NO: 15 
               
               
                 SG16 
                 SEQ ID 
                 3485 
                 IGFBP2 
                 Binding protein to the growth factor similar 
               
               
                   
                 NO: 16 
                   
                   
                 to insulin 2, 36 kDa 
               
               
                 SG17 
                 SEQ ID 
                 10397 
                 NDRG1 
                 Gene regulated downstream by N-myc 1 
               
               
                   
                 NO: 17 
               
               
                 SG18 
                 SEQ ID 
                 11328 
                 FKBP9 
                 FK506 9-binding protein, 63 kDa 
               
               
                   
                 NO: 18 
               
               
                 SG19 
                 SEQ ID 
                 10241 
                 NDP52 
                 protein of the nuclear domain 10 
               
               
                   
                 NO: 19 
               
               
                 SG20 
                 SEQ ID 
                 2171 
                 FABP5 
                 protein which binds to fatty acids 5 
               
               
                   
                 NO: 20 
                   
                   
                 (associated to psoriasis) 
               
               
                 SG21 
                 SEQ ID 
                 10160 
                 FARP1 
                 protein with FERM, RhoGEF (ARHGEF) 
               
               
                   
                 NO: 21 
                   
                   
                 and pleckstrin 1 domains (derived from 
               
               
                   
                   
                   
                   
                 chrondrocytes) 
               
               
                 SG22 
                 SEQ ID 
                 5228 
                 PGF 
                 Placental growth factor, protein related to 
               
               
                   
                 NO: 22 
                   
                   
                 the endothelial growth factor 
               
               
                 SG23 
                 SEQ ID 
                 2665 
                 GDI2 
                 GDP 2 dissociation inhibitor 
               
               
                   
                 NO: 23 
               
               
                 SG24 
                 SEQ ID 
                 8407 
                 TAGLN2 
                 transgelin 2 
               
               
                   
                 NO: 24 
               
               
                 SG25 
                 SEQ ID 
                 645 
                 BLVRB 
                 biliverdin reductase B (flavin reductase 
               
               
                   
                 NO: 25 
                   
                   
                 (NADPH)) 
               
               
                 SG26 
                 SEQ ID 
                 5692 
                 PSMB4 
                 subunit of proteasome (prosome, 
               
               
                   
                 NO: 26 
                   
                   
                 macropain), beta-type, 4 
               
               
                 SG27 
                 SEQ ID 
                 4070 
                 TACSTD2 
                 transducer of the calcium signal associated 
               
               
                   
                 NO: 27 
                   
                   
                 to tumours 2 
               
               
                 SG28 
                 SEQ ID 
                 6921 
                 TCEB1 
                 Elongation factor of transcription B (SIII), 
               
               
                   
                 NO: 28 
                   
                   
                 polypeptide 1 (15 kDa, elongin C) 
               
               
                 SG29 
                 SEQ ID 
                 1915 
                 EEF1A1 
                 elongation factor in the eukaryotic 
               
               
                   
                 NO: 29 
                   
                   
                 translation 1 alpha 1 
               
               
                 SG30 
                 SEQ ID 
                 3020 
                 H3F3A 
                 histone H3, family 3A 
               
               
                   
                 NO: 30 
               
               
                 SG31 
                 SEQ ID 
                 4953 
                 ODC1 
                 ornithine decarboxylase 1 
               
               
                   
                 NO: 31 
               
               
                 SG32 
                 SEQ ID 
                 7520 
                 XRCC5 
                 Of repair of X rays which complement the 
               
               
                   
                 NO: 32 
                   
                   
                 defective repair in Chinese hamster cells 5 
               
               
                   
                   
                   
                   
                 (reconnection of breakages in the double 
               
               
                   
                   
                   
                   
                 helix; autoantigen Ku, 80 kDa) 
               
               
                 SG33 
                 SEQ ID 
                 3486 
                 IGFBP3 
                 binding protein to growth factor similar to 
               
               
                   
                 NO: 33 
                   
                   
                 insulin 3 
               
               
                 SG34 
                 SEQ ID 
                 4691 
                 NCL 
                 nucleolin 
               
               
                   
                 NO: 34 
               
               
                 SG35 
                 SEQ ID 
                 6273 
                 S100A2 
                 calcium S100 A2-binding protein 
               
               
                   
                 NO: 35 
               
               
                 SG36 
                 SEQ ID 
                 6152 
                 RPL24 
                 ribosomal protein L24 
               
               
                   
                 NO: 36 
               
               
                 SG37 
                 SEQ ID 
                 2697 
                 GJA1 
                 Bone filling protein, alpha 1, 43 kDa 
               
               
                   
                 NO: 37 
                   
                   
                 (connexin 43) 
               
               
                 SG38 
                 SEQ ID 
                 2990 
                 GUSB 
                 glucuronidase, beta 
               
               
                   
                 NO: 38 
               
               
                 SG39 
                 SEQ ID 
                 3292 
                 HSD17B1 
                 hydroxysteroid (17-beta) dehydrogenase 1 
               
               
                   
                 NO: 39 
               
               
                 SG40 
                 SEQ ID 
                 6439 
                 SFTPB 
                 surfactant protein, associated to lung B 
               
               
                   
                 NO: 40 
               
               
                 SG41 
                 SEQ ID 
                 6147 
                 RPL23A 
                 ribosomal protein L23a 
               
               
                   
                 NO: 41 
               
               
                 SG42 
                 SEQ ID 
                 1466 
                 CSRP2 
                 protein rich in cysteine and glycine 2 
               
               
                   
                 NO: 42 
               
               
                 SG43 
                 SEQ ID 
                 1525 
                 CXADR 
                 receptor of the coxsackie virus and 
               
               
                   
                 NO: 43 
                   
                   
                 adenovirus 
               
               
                 SG44 
                 SEQ ID 
                 1937 
                 EEF1G 
                 elongation factor of eukartyotic 1 gamma 
               
               
                   
                 NO: 44 
                   
                   
                 elongation 
               
               
                 SG45 
                 SEQ ID 
                 1164 
                 CKS2 
                 subunit regulating the kinase CDC28 2 
               
               
                   
                 NO: 45 
                   
                   
                 protein 
               
               
                 SG46 
                 SEQ ID 
                 1288 
                 COL4A6 
                 collagen, type IV, alpha 6 
               
               
                   
                 NO: 46 
               
               
                 SG47 
                 SEQ ID 
                 1410 
                 CRYAB 
                 crystalline, alpha B 
               
               
                   
                 NO: 47 
               
               
                 SG48 
                 SEQ ID 
                 1537 
                 CYC1 
                 cytochrome c-1 
               
               
                   
                 NO: 48 
               
               
                 SG49 
                 SEQ ID 
                 2342 
                 FNTB 
                 farnesyltransferase, CAAX box, beta 
               
               
                   
                 NO: 49 
               
               
                 SG50 
                 SEQ ID 
                 2805 
                 GOT1 
                 glutamic-oxaloacetic transaminase 1, 
               
               
                   
                 NO: 50 
                   
                   
                 soluble (aminotransferase 1 aspartate) 
               
               
                 SG51 
                 SEQ ID 
                 3963 
                 LGALS7 
                 Lectin, which binds to galactosides, soluble, 
               
               
                   
                 NO: 51 
                   
                   
                 7 (galectin 7) 
               
               
                 SG52 
                 SEQ ID 
                 5268 
                 SERPINB5 
                 Serine (or cysteine) inhibitor proteinase, 
               
               
                   
                 NO: 52 
                   
                   
                 clade B (ovalbumin, member 5 
               
               
                 SG53 
                 SEQ ID 
                 5705 
                 PSMC5 
                 Subunit of proteasome (prosome, 
               
               
                   
                 NO: 53 
                   
                   
                 macropain) 26S, ATPase, 5 
               
               
                 SG54 
                 SEQ ID 
                 5764 
                 PTN 
                 pleiotrophin (growth factor of bonding to 
               
               
                   
                 NO: 54 
                   
                   
                 heparin 8, growth promoter factor of 
               
               
                   
                   
                   
                   
                 neurites 1) 
               
               
                 SG55 
                 SEQ ID 
                 5932 
                 RBBP8 
                 Retinoblastoma 8-binding protein 
               
               
                   
                 NO: 55 
               
               
                 SG56 
                 SEQ ID 
                 5996 
                 RGS1 
                 Regulator of the signalling by proteins G 1 
               
               
                   
                 NO: 56 
               
               
                 SG57 
                 SEQ ID 
                 6256 
                 RXRA 
                 Retinoid X receptor, alpha 
               
               
                   
                 NO: 57 
               
               
                 SG58 
                 SEQ ID 
                 6392 
                 SDHD 
                 succinate dehydrogenase complex, subunit 
               
               
                   
                 NO: 58 
                   
                   
                 D, integral membrane protein 
               
               
                 SG59 
                 SEQ ID 
                 6415 
                 SEPW1 
                 selenoprotein W, 1 
               
               
                   
                 NO: 59 
               
               
                 SG60 
                 SEQ ID 
                 6742 
                 SSBP1 
                 binding protein to single-strand DNA 1 
               
               
                   
                 NO: 60 
               
               
                 SG61 
                 SEQ ID 
                 7009 
                 TEGT 
                 transcript of gene increased in the testicle 
               
               
                   
                 NO: 61 
                   
                   
                 (BAX 1 inhibitor) 
               
               
                 SG62 
                 SEQ ID 
                 8341 
                 HIST1H2BN 
                 histone 1, H2bn 
               
               
                   
                 NO: 62 
               
               
                 SG63 
                 SEQ ID 
                 8678 
                 BECN1 
                 beclin 1 (protein similar to myosin which 
               
               
                   
                 NO: 63 
                   
                   
                 interacts with BCL2, of twisted helix) 
               
               
                 SG64 
                 SEQ ID 
                 310 
                 ANXA7 
                 annexin A7 
               
               
                   
                 NO: 64 
               
               
                 SG65 
                 SEQ ID 
                 4694 
                 NDUFA1 
                 Alpha subcomplex of NADH 
               
               
                   
                 NO: 65 
                   
                   
                 dehydrogenase (ubiquinone) 1, 1, 
               
               
                 SG66 
                 SEQ ID 
                 9181 
                 ARHGEF2 
                 guanine rho/rac exchange factor (GEF) 2 
               
               
                   
                 NO: 66 
               
               
                 SG67 
                 SEQ ID 
                 9315 
                 C5orfl3 
                 Open reading frame 13 of chromosome 5 
               
               
                   
                 NO: 67 
               
               
                 SG68 
                 SEQ ID 
                 7494 
                 XBP1 
                 X 1 box-binding protein 
               
               
                   
                 NO: 68 
               
               
                 SG69 
                 SEQ ID 
                 9636 
                 G1P2 
                 protein inducible by the alpha interferon 
               
               
                   
                 NO: 69 
                   
                   
                 (clone IFI-15K) 
               
               
                 SG70 
                 SEQ ID 
                 2746 
                 GLUD1 
                 glutamate dehydrogenase 1 
               
               
                   
                 NO: 70 
               
               
                 SG71 
                 SEQ ID 
                 6273 
                 S100A2 
                 calcium S100 A2-binding protein 
               
               
                   
                 NO: 71 
               
               
                 SG72 
                 SEQ ID 
                 3927 
                 LASP1 
                 LIM and SH3 1 protein 
               
               
                   
                 NO: 72 
               
               
                 SG73 
                 SEQ ID 
                 10630 
                 TIA-2 
                 glycoprotein associated to the lung cell 
               
               
                   
                 NO: 73 
                   
                   
                 membrane type I 
               
               
                 SG74 
                 SEQ ID 
                 10857 
                 PGRMC1 
                 Membrane component of the progesterone 
               
               
                   
                 NO: 74 
                   
                   
                 1 receptor 
               
               
                 SG75 
                 SEQ ID 
                 7542 
                 ZFPL1 
                 protein similar to that of zinc finger 1 
               
               
                   
                 NO: 75 
               
               
                 SG76 
                 SEQ ID 
                 11184 
                 MAP4K1 
                 Kinase protein activated by mitogens 1 
               
               
                   
                 NO: 76 
               
               
                 SG77 
                 SEQ ID 
                 6772 
                 STAT1 
                 Signal transducer and transcription activator 
               
               
                   
                 NO: 77 
                   
                   
                 1, 91 kDa 
               
               
                 SG78 
                 SEQ ID 
                 3189 
                 HNRPH3 
                 Heterogeneous nuclear ribonucleoprotein 
               
               
                   
                 NO: 78 
                   
                   
                 H3 (2H9) 
               
               
                 SG79 
                 SEQ ID 
                 10330 
                 TMEM4 
                 Transmembrane protein 4 
               
               
                   
                 NO: 79 
               
               
                 SG80 
                 SEQ ID 
                 9766 
                 KIAA0247 
                 KIAA0247 
               
               
                   
                 NO: 80 
               
               
                 SG81 
                 SEQ ID 
                 25907 
                 RIS1 
                 of senescence induced by Ras 1 
               
               
                   
                 NO: 81 
               
               
                 SG82 
                 SEQ ID 
                 51593 
                 ARS2 
                 Arsenate-resistant protein ARS2 
               
               
                   
                 NO: 82 
               
               
                 SG83 
                 SEQ ID 
                 771 
                 CA12 
                 Carbonic anhydrase XII 
               
               
                   
                 NO: 83 
               
               
                 SG84 
                 SEQ ID 
                 1933 
                 EEF1B2 
                 elongation factor of the eukaryotic 1 beta 2 
               
               
                   
                 NO: 84 
                   
                   
                 translation 
               
               
                 SG85 
                 SEQ ID 
                 28951 
                 TRIB2 
                 homologue to tribbles 2 ( Drosophila ) 
               
               
                   
                 NO: 85 
               
               
                 SG86 
                 SEQ ID 
                 79065 
                 FLJ22169 
                 similar to that of autophagy 9 APG9 1 ( S. cerevisiae ) 
               
               
                   
                 NO: 86 
               
               
                 SG87 
                 SEQ ID 
                 440 
                 ASNS 
                 asparagine synthetase 
               
               
                   
                 NO: 87 
               
               
                 SG88 
                 SEQ ID 
                 260294 
                 WBSCR20C 
                 Chromosome region 20C of Williams 
               
               
                   
                 NO: 88 
                   
                   
                 Beuren syndrome 
               
               
                 SG89 
                 SEQ ID 
                 10327 
                 AKR1A1 
                 member A1 of the aldo-keto reductase 1 
               
               
                   
                 NO: 89 
                   
                   
                 family (aldehyde reductase) 
               
               
                 SG90 
                 SEQ ID 
                 6698 
                 SPRR1A 
                 Small proline 1A-rich protein 
               
               
                   
                 NO: 90 
               
               
                 SG91 
                 SEQ ID 
                 1947 
                 EFNB1 
                 ephrin-B1 
               
               
                   
                 NO: 91 
               
               
                 SG92 
                 SEQ ID 
                 6193 
                 RPS5 
                 ribosomal protein S5 
               
               
                   
                 NO: 92 
               
               
                 SG93 
                 SEQ ID 
                 6203 
                 RPS9 
                 ribosomal protein S9 
               
               
                   
                 NO: 93 
               
               
                 SG94 
                 SEQ ID 
                 6139 
                 RPL17 
                 ribosomal protein L17 
               
               
                   
                 NO: 94 
               
               
                 SG95 
                 SEQ ID 
                 2114 
                 ETS2 
                 homologue to oncogene E26 of the 
               
               
                   
                 NO: 95 
                   
                   
                 erythroblastosis virus v-ets 2 (avian) 
               
               
                 SG96 
                 SEQ ID 
                 1975 
                 EIF4B 
                 initiation factor of the eukaryotic translation 
               
               
                   
                 NO: 96 
                   
                   
                 4B 
               
               
                 SG97 
                 SEQ ID 
                 7791 
                 ZYX 
                 Zyxin 
               
               
                   
                 NO: 97 
               
               
                 SG98 
                 SEQ ID 
                 23214 
                 XPO6 
                 exportin 6 
               
               
                   
                 NO: 98 
               
               
                 SG99 
                 SEQ ID 
                 285148 
                 LOC285148 
                 Hypothetical protein LOC285148 
               
               
                   
                 NO: 99 
               
               
                 SG100 
                 SEQ ID 
                 8209 
                 C21orf33 
                 open reading frame 33 of chromosome 21 
               
               
                   
                 NO: 100 
               
               
                 SG101 
                 SEQ ID 
                 1936 
                 EEF1D 
                 elongation factor of the eukaryotic 
               
               
                   
                 NO: 101 
                   
                   
                 translation 1 delta (guanine nucleotide 
               
               
                   
                   
                   
                   
                 exchange protein) 
               
               
                 SG102 
                 SEQ ID 
                 26986 
                 PABPC1 
                 poly(A)-binding protein, cytoplasmic 1 
               
               
                   
                 NO: 102 
               
               
                 SG103 
                 SEQ ID 
                 5930 
                 RBBP6 
                 retinoblastoma 6-binding protein 
               
               
                   
                 NO: 103 
               
               
                 SG104 
                 SEQ ID 
                 3265 
                 HRAS 
                 homologue to the viral oncogene of the 
               
               
                   
                 NO: 104 
                   
                   
                 Harvey v-Ha-ras rat sarcoma 
               
               
                 SG105 
                 SEQ ID 
                 23163 
                 GGA3 
                 ARF-binding protein, which contains 
               
               
                   
                 NO: 105 
                   
                   
                 gamma-adaptin, associated to golgi 
               
               
                 SG106 
                 SEQ ID 
                 1072 
                 CFL1 
                 cophilin 1 (non-muscular) 
               
               
                   
                 NO: 106 
               
               
                 SG107 
                 SEQ ID 
                 8668 
                 EIF3S2 
                 initiation factor of the eukaryotic translation 
               
               
                   
                 NO: 107 
                   
                   
                 3, subunit 2 beta, 36 kDa 
               
               
                 SG108 
                 SEQ ID 
                 3875 
                 KRT18 
                 keratine 18 
               
               
                   
                 NO: 108 
               
               
                 SG109 
                 SEQ ID 
                 3480 
                 IGFIR 
                 growth factor receptor similar to insulin 1 
               
               
                   
                 NO: 109 
               
               
                 SG110 
                 SEQ ID 
                 3576 
                 IL8 
                 Interleukin 8 
               
               
                   
                 NO: 110 
               
               
                 SG111 
                 SEQ ID 
                 3659 
                 IRF1 
                 Interferon regulating factor 1 
               
               
                   
                 NO: 111 
               
               
                 SG112 
                 SEQ ID 
                 3660 
                 IRF2 
                 Interferon regulating factor 2 
               
               
                   
                 NO: 112 
               
               
                 SG113 
                 SEQ ID 
                 4067 
                 LYN 
                 Homologue to the oncogene related to the 
               
               
                   
                 NO: 113 
                   
                   
                 viral sarcoma of Yamaguchi V-yes-1 
               
               
                 SG114 
                 SEQ ID 
                 4069 
                 LYZ 
                 Lysozyme (renal amiloidosis) 
               
               
                   
                 NO: 114 
               
               
                 SG115 
                 SEQ ID 
                 4792 
                 NFKB1A 
                 Nuclear factor of the gene enhancer of the 
               
               
                   
                 NO: 115 
                   
                   
                 kappa light polypeptide in B L-lymphocytes 
               
               
                   
                   
                   
                   
                 (p105) 
               
               
                 SG116 
                 SEQ ID 
                 4150 
                 MAZ 
                 Zinc finger protein associated to MYC 
               
               
                   
                 NO: 116 
                   
                   
                 (transcription factor of binding to purins) 
               
               
                 SG117 
                 SEQ ID 
                 973 
                 CD79A 
                 Antigen CD79A (associated to alpha 
               
               
                   
                 NO: 117 
                   
                   
                 immunoglobulins) 
               
               
                 SG118 
                 SEQ ID 
                 4172 
                 MCM3 
                 Deficient maintenance of minichromosomes 
               
               
                   
                 NO: 118 
                   
                   
                 ( S. cerevisiae ) 3 
               
               
                 SG119 
                 SEQ ID 
                 421 
                 MEIS1 
                 Homologue to Meis1 (mouse) 
               
               
                   
                 NO: 119 
               
               
                 SG120 
                 SEQ ID 
                 5657 
                 PRTN3 
                 Proteinase 3 (serine proteinase, 
               
               
                   
                 NO: 120 
                   
                   
                 autoantigen of Wegener&#39;s granulomatosis 
               
               
                   
                   
                   
                   
                 of neutrophils) 
               
               
                 SG121 
                 SEQ ID 
                 4313 
                 MMP2 
                 Metalloproteinase of matrix 2 (gelatinase A, 
               
               
                   
                 NO: 121 
                   
                   
                 72 kD gelatinase of, 72 kD collagenase type 
               
               
                   
                   
                   
                   
                 IV) 
               
               
                 SG122 
                 SEQ ID 
                 4316 
                 MMP7 
                 Metalloproteinase of matrix 7 (matrilysin, 
               
               
                   
                 NO: 122 
                   
                   
                 uterine) 
               
               
                 SG123 
                 SEQ ID 
                 4317 
                 MMP8 
                 Metalloproteinase of matrix 8 (neutrophil 
               
               
                   
                 NO: 123 
                   
                   
                 collagenase) 
               
               
                 SG124 
                 SEQ ID 
                 1796 
                 DOK1 
                 Adapter protein 1, 62 kD (downstream 
               
               
                   
                 NO: 124 
                   
                   
                 respect to thyrosine kinase 1) 
               
               
                 SG125 
                 SEQ ID 
                 5154 
                 PDGFA 
                 Alpha polypeptide of the platelet-derived 
               
               
                   
                 NO: 125 
                   
                   
                 growth factor 
               
               
                 SG126 
                 SEQ ID 
                 5617 
                 PRL 
                 Prolactin 
               
               
                   
                 NO: 126 
               
               
                 SG127 
                 SEQ ID 
                 5894 
                 RAF1 
                 Homologue to the viral oncogene of murine 
               
               
                   
                 NO: 127 
                   
                   
                 leukemia V-raf-1 1 
               
               
                 SG128 
                 SEQ ID 
                 5915 
                 RARB 
                 Retinoic acid receptor, beta 
               
               
                   
                 NO: 128 
               
               
                 SG129 
                 SEQ ID 
                 4985 
                 OPRD1 
                 Opioid receptor, delta 1 
               
               
                   
                 NO: 129 
               
               
                 SG130 
                 SEQ ID 
                 5979 
                 RET 
                 proto-oncogene ret (multiple endocrine 
               
               
                   
                 NO: 130 
                   
                   
                 neoplasia and medullary thyroid carcinoma 
               
               
                   
                   
                   
                   
                 1, Hirschsprung&#39;s disease) 
               
               
                 SG131 
                 SEQ ID 
                 6720 
                 SREBF1 
                 Transcription factor of binding to sterol 
               
               
                   
                 NO: 131 
                   
                   
                 regulatory elements 1 
               
               
                 SG132 
                 SEQ ID 
                 7124 
                 TNF 
                 Tumour necrosing factor (TNF superfamily, 
               
               
                   
                 NO: 132 
                   
                   
                 member 2) 
               
               
                 SG133 
                 SEQ ID 
                 7013 
                 TERF1 
                 Binding factor to telomeric repetitions 
               
               
                   
                 NO: 133 
                   
                   
                 (which interact with NIMA) 1 
               
               
                 SG134 
                 SEQ ID 
                 7412 
                 VCAM1 
                 Molecule of adhesion to vascular cells 1 
               
               
                   
                 NO: 134 
               
               
                 SG135 
                 SEQ ID 
                 539 
                 ATP5O 
                 ATP synthase, H+ carrier, mitochondrial F1 
               
               
                   
                 NO: 135 
                   
                   
                 complex, subunit O (protein which gives 
               
               
                   
                   
                   
                   
                 sensitivity to oligomycin) 
               
               
                 SG136 
                 SEQ ID 
                 959 
                 TNFSF5 
                 Tumour necrosing factor (ligand) 
               
               
                   
                 NO: 136 
                   
                   
                 superfamily, member 5 (hyper-IgM 
               
               
                   
                   
                   
                   
                 syndrome) 
               
               
                 SG137 
                 SEQ ID 
                 5432 
                 POLR2C 
                 Polypeptide C (directed at DNA) of the RNA 
               
               
                   
                 NO: 137 
                   
                   
                 polymerase II (33 kD) 
               
               
                 SG138 
                 SEQ ID 
                 8398 
                 PLA2G6 
                 Phospholipase A2, group VI (cytosolic, 
               
               
                   
                 NO: 138 
                   
                   
                 calcium-dependent) 
               
               
                 SG139 
                 SEQ ID 
                 908 
                 CCT6A 
                 TCP1 which contains chaperonin, subunit 
               
               
                   
                 NO: 139 
                   
                   
                 6A (zeta 1) 
               
               
                 SG140 
                 SEQ ID 
                 5160 
                 PDHA1 
                 Pyruvate dehydrogenase (lipoamide) alpha 1 
               
               
                   
                 NO: 140 
               
               
                 SG141 
                 SEQ ID 
                 3939 
                 LADH 
                 Lactate dehydrogenase A 
               
               
                   
                 NO: 141 
               
               
                 SG142 
                 SEQ ID 
                 6628 
                 SNRPB 
                 Polypeptides B and B1 of the small nuclear 
               
               
                   
                 NO: 142 
                   
                   
                 ribonucleoprotein 
               
               
                 SG143 
                 SEQ ID 
                 6628 
                 SNRPB 
                 Polypeptides B and B1 of the small nuclear 
               
               
                   
                 NO: 143 
                   
                   
                 ribonucleoprotein 
               
               
                 SG144 
                 SEQ ID 
                 3014 
                 H2AFX 
                 Histone family H2A, member X 
               
               
                   
                 NO: 144 
               
               
                 SG145 
                 SEQ ID 
                 51253 
                 MRPL37 
                 Mitochondrial ribosomal protein L37 
               
               
                   
                 NO: 145 
               
               
                 SG146 
                 SEQ ID 
                 11065 
                 UBE2C 
                 Enzyme which conjugates with ubiquin E2C 
               
               
                   
                 NO: 146 
               
               
                 SG147 
                 SEQ ID 
                 6188 
                 RPS3 
                 Ribosomal protein S3A 
               
               
                   
                 NO: 147 
               
               
                 SG148 
                 SEQ ID 
                 216 
                 ALDH1A1 
                 Aldehyde dehydrogenase 1 family, member 
               
               
                   
                 NO: 148 
                   
                   
                 A1 
               
               
                 SG149 
                 SEQ ID 
                 10962 
                 AF1q 
                 Lymphoid/myeloid or leukemia or of mixed 
               
               
                   
                 NO: 149 
                   
                   
                 line (homologue to trithorax,  Drosophila ); 
               
               
                   
                   
                   
                   
                 translocated to 11 
               
               
                 SG150 
                 SEQ ID 
                 861 
                 RUNX1 
                 Runt 1-related transcription (acute myeloid 
               
               
                   
                 NO: 150 
                   
                   
                 leukemia 1; oncogene aml1) 
               
               
                 SG151 
                 SEQ ID 
                 4603 
                 MYBL1 
                 Similar to the homologue of the viral 
               
               
                   
                 NO: 151 
                   
                   
                 oncogene of avian myeloblastisis V-myb 1 
               
               
                 SG152 
                 SEQ ID 
                 309 
                 ANXA6 
                 Annexin A6 
               
               
                   
                 NO: 152 
               
               
                 SG153 
                 SEQ ID 
                 238 
                 ALK 
                 Anaplastic lymphoma kinase (Ki-1) 
               
               
                   
                 NO: 153 
               
               
                 SG154 
                 SEQ ID 
                 4332 
                 MNDA 
                 Antigen for nuclear differentiation myeloid 
               
               
                   
                 NO: 154 
                   
                   
                 cells 
               
               
                 SG155 
                 SEQ ID 
                 317 
                 APAF1 
                 Apoptotic protease activator factor 
               
               
                   
                 NO: 155 
               
               
                 SG156 
                 SEQ ID 
                 330 
                 BIRC3 
                 which contains IAP repetitions of 
               
               
                   
                 NO: 156 
                   
                   
                 baculovirus 3 
               
               
                 SG157 
                 SEQ ID 
                 368 
                 ABCC6 
                 ATP-binding module, subfamily C 
               
               
                   
                 NO: 157 
                   
                   
                 (CFTR/MRP), member 6 
               
               
                 SG158 
                 SEQ ID 
                 471 
                 ATIC 
                 5-aminoimidazol-4-carboxamide 
               
               
                   
                 NO: 158 
                   
                   
                 ribonucleotide formyltransferase/IMP 
               
               
                   
                   
                   
                   
                 cyclohydrolase 
               
               
                 SG159 
                 SEQ ID 
                 472 
                 ATM 
                 Mutated ataxia-telangiectasia (includes 
               
               
                   
                 NO: 159 
                   
                   
                 complementary groups A, C and D) 
               
               
                 SG160 
                 SEQ ID 
                 581 
                 BAX 
                 protein X associated to BCL2 
               
               
                   
                 NO: 160 
               
               
                 SG161 
                 SEQ ID 
                 595 
                 CCND1 
                 Cyclin D1 (PRAD1: parathyroidal 
               
               
                   
                 NO: 161 
                   
                   
                 adenomatosis 1) 
               
               
                 SG162 
                 SEQ ID 
                 596 
                 BCL2 
                 CLL/lymphoma of B 2 lymphocytes 
               
               
                   
                 NO: 162 
               
               
                 SG163 
                 SEQ ID 
                 602 
                 BCL3 
                 CLL/lymphoma of B 3 lymphocytes 
               
               
                   
                 NO: 163 
               
               
                 SG164 
                 SEQ ID 
                 604 
                 BCL6 
                 CLL/lymphoma of B 6 lymphocytes (protein 
               
               
                   
                 NO: 164 
                   
                   
                 with zinc fingers 51) 
               
               
                 SG165 
                 SEQ ID 
                 605 
                 BCL7A 
                 CLL/lymphoma of B 7A lymphocytes 
               
               
                   
                 NO: 165 
               
               
                 SG166 
                 SEQ ID 
                 9275 
                 BCL7b 
                 CLL/lymphoma of B 7B lymphocytes 
               
               
                   
                 NO: 166 
               
               
                 SG167 
                 SEQ ID 
                 8915 
                 BCL10 
                 CLL/lymphoma of B 10 lymphocytes 
               
               
                   
                 NO: 167 
               
               
                 SG168 
                 SEQ ID 
                 598 
                 BCL2L1 
                 similar to BCL2 1 
               
               
                   
                 NO: 168 
               
               
                 SG169 
                 SEQ ID 
                 613 
                 BCR 
                 Grouping breaking point region 
               
               
                   
                 NO: 169 
               
               
                 SG170 
                 SEQ ID 
                 613 
                 BCR 
                 Grouping breaking point region 
               
               
                   
                 NO: 170 
               
               
                 SG171 
                 SEQ ID 
                 10215 
                 OLIG2 
                 Transcription factor of oligodendrocytes 2 
               
               
                   
                 NO: 171 
                   
                   
                 line 
               
               
                 SG172 
                 SEQ ID 
                 638 
                 BIK 
                 Mortal factor which interacts with BCL2 
               
               
                   
                 NO: 172 
                   
                   
                 (apoptosis inducer) 
               
               
                 SG173 
                 SEQ ID 
                 10018 
                 BCL2LAA 
                 Similar to BCL2 (which facilitates 
               
               
                   
                 NO: 173 
                   
                   
                 apoptosis) 
               
               
                 SG174 
                 SEQ ID 
                 648 
                 BMI1 
                 Homologue to the viral oncogene of murine 
               
               
                   
                 NO: 174 
                   
                   
                 leukemia (bmi-1) 
               
               
                 SG175 
                 SEQ ID 
                 642 
                 BLMH 
                 bleomycin hydrolase 
               
               
                   
                 NO: 175 
               
               
                 SG176 
                 SEQ ID 
                 643 
                 BLR1 
                 Burkitt 1 lymphoma receptor, GTP-binding 
               
               
                   
                 NO: 176 
                   
                   
                 protein 
               
               
                 SG177 
                 SEQ ID 
                 3381 
                 IBSP 
                 Integrin-binding sialoprotein (bone 
               
               
                   
                 NO: 177 
                   
                   
                 sialoprotein bone sialoprotein II) 
               
               
                 SG178 
                 SEQ ID 
                 694 
                 BTG1 
                 Gene of translocation of B lymphocytes, 
               
               
                   
                 NO: 178 
                   
                   
                 anti-proliferative 
               
               
                 SG179 
                 SEQ ID 
                 699 
                 BUB1 
                 Disinhibited budding by benzimidazoles 1 
               
               
                   
                 NO: 179 
                   
                   
                 (homologue of yeasts) 
               
               
                 SG180 
                 SEQ ID 
                 25 
                 ABL1 
                 homologue to the viral oncogene of that of 
               
               
                   
                 NO: 180 
                   
                   
                 Abelson&#39;s murine leukemia v-abl 1 
               
               
                 SG181 
                 SEQ ID 
                 834 
                 CASP1 
                 caspase 1, apoptosis-related cysteine 
               
               
                   
                 NO: 181 
                   
                   
                 protease (interleukin 1, beta, convertase) 
               
               
                 SG182 
                 SEQ ID 
                 836 
                 CASP3 
                 caspase 3, apoptosis-related cysteine 
               
               
                   
                 NO: 182 
                   
                   
                 protease 
               
               
                 SG183 
                 SEQ ID 
                 837 
                 CASP4 
                 caspase 4, apoptosis-related cysteine 
               
               
                   
                 NO: 183 
                   
                   
                 protease 
               
               
                 SG184 
                 SEQ ID 
                 838 
                 CASP5 
                 caspase 5, apoptosis-related cysteine 
               
               
                   
                 NO: 184 
                   
                   
                 protease 
               
               
                 SG185 
                 SEQ ID 
                 839 
                 CASP6 
                 caspase 6, apoptosis-related cysteine 
               
               
                   
                 NO: 185 
                   
                   
                 protease 
               
               
                 SG186 
                 SEQ ID 
                 840 
                 CASP7 
                 caspase 7, apoptosis-related cysteine 
               
               
                   
                 NO: 186 
                   
                   
                 protease 
               
               
                 SG187 
                 SEQ ID 
                 841 
                 CASP8 
                 caspase 8, apoptosis-related cysteine 
               
               
                   
                 NO: 187 
                   
                   
                 protease 
               
               
                 SG188 
                 SEQ ID 
                 842 
                 CASP9 
                 caspase 9, apoptosis-related cysteine 
               
               
                   
                 NO: 188 
                   
                   
                 protease 
               
               
                 SG189 
                 SEQ ID 
                 865 
                 CBFB 
                 Nucleus binding factor, beta subunit 
               
               
                   
                 NO: 189 
               
               
                 SG190 
                 SEQ ID 
                 800 
                 CALD1 
                 Caldesmon 1 
               
               
                   
                 NO: 190 
               
               
                 SG191 
                 SEQ ID 
                 831 
                 CAST 
                 Calpastatin 
               
               
                   
                 NO: 191 
               
               
                 SG192 
                 SEQ ID 
                 993 
                 CDC25A 
                 Cell division cycle 25A 
               
               
                   
                 NO: 192 
               
               
                 SG193 
                 SEQ ID 
                 994 
                 CDC25B 
                 Cell division cycle 25B 
               
               
                   
                 NO: 193 
               
               
                 SG194 
                 SEQ ID 
                 914 
                 CD2 
                 Antigen CD2 (p50), sheep red blood cell 
               
               
                   
                 NO: 194 
                   
                   
                 receptor 
               
               
                 SG195 
                 SEQ ID 
                 916 
                 CD3E 
                 Antigen CD3E, epilson polypeptide 
               
               
                   
                 NO: 195 
                   
                   
                 (complex TiT3) 
               
               
                 SG196 
                 SEQ ID 
                 920 
                 CD4 
                 Antigen CD4 (p55) 
               
               
                   
                 NO: 196 
               
               
                 SG197 
                 SEQ ID 
                 921 
                 CD5 
                 Antigen CD5 (p56-62) 
               
               
                   
                 NO: 197 
               
               
                 SG198 
                 SEQ ID 
                 923 
                 CD6 
                 Antigen CD6 
               
               
                   
                 NO: 198 
               
               
                 SG199 
                 SEQ ID 
                 924 
                 CD7 
                 Antigen CD7 (p41) 
               
               
                   
                 NO: 199 
               
               
                 SG200 
                 SEQ ID 
                 925 
                 CD8 
                 Antigen CD8, alpha polypeptide(p32) 
               
               
                   
                 NO: 200 
               
               
                 SG201 
                 SEQ ID 
                 928 
                 CD9 
                 Antigen CD9 (p24) 
               
               
                   
                 NO: 201 
               
               
                 SG202 
                 SEQ ID 
                 4311 
                 MME 
                 Membrane metalloendopeptidase (neutral 
               
               
                   
                 NO: 202 
                   
                   
                 endopeptidase, encephalinase, CALLA, 
               
               
                   
                   
                   
                   
                 CD10) 
               
               
                 SG203 
                 SEQ ID 
                 3683 
                 ITGAL 
                 Integrin, alpha L (antigen CD11A (p180), 
               
               
                   
                 NO: 203 
                   
                   
                 antigen associated to the function of 
               
               
                   
                   
                   
                   
                 lymphocytes 1; alpha polypeptide) 
               
               
                 SG204 
                 SEQ ID 
                 3684 
                 ITGAM 
                 Integrin, alpha M (complement 3 
               
               
                   
                 NO: 204 
                   
                   
                 component receptor, alpha; also known as 
               
               
                   
                   
                   
                   
                 CD11b (p170), polypeptide of the 
               
               
                   
                   
                   
                   
                 macrophage alpha antigen) 
               
               
                 SG205 
                 SEQ ID 
                 3687 
                 ITGAX 
                 Integrin, alpha X (antigen CD11C (p150), 
               
               
                   
                 NO: 205 
                   
                   
                 alpha polypeptide) 
               
               
                 SG206 
                 SEQ ID 
                 90 
                 ANPEP 
                 Alanyl-(membrane)aminopeptidase 
               
               
                   
                 NO: 206 
                   
                   
                 (aminopeptidase N, aminopeptidase M, 
               
               
                   
                   
                   
                   
                 microsomal aminopeptidase, CD13, p150) 
               
               
                 SG207 
                 SEQ ID 
                 929 
                 CD14 
                 Antigen CD14 
               
               
                   
                 NO: 207 
               
               
                 SG208 
                 SEQ ID 
                 6401 
                 SELE 
                 Selectin E (endothelial adhesion molecule 
               
               
                   
                 NO: 208 
                   
                   
                 1) 
               
               
                 SG209 
                 SEQ ID 
                 2214 
                 FCGR3A 
                 Low-affinity receptor IIIa for the Fc fragment 
               
               
                   
                 NO: 209 
                   
                   
                 of IgG (CD16) 
               
               
                 SG210 
                 SEQ ID 
                 2215 
                 FCGR3B 
                 Low-affinity receptor IIIb for the Fc fragment 
               
               
                   
                 NO: 210 
                   
                   
                 of IgG (CD16) 
               
               
                 SG211 
                 SEQ ID 
                 3689 
                 ITGB2 
                 Integrin, beta 2 (antigen CD18 (p95), 
               
               
                   
                 NO: 211 
                   
                   
                 antigen associated to the function of the 
               
               
                   
                   
                   
                   
                 lymphocytes 1; beta subunit of the 
               
               
                   
                   
                   
                   
                 microphage 1 (mac-1) antigen) 
               
               
                 SG212 
                 SEQ ID 
                 930 
                 CD19 
                 Antigen CD19 
               
               
                   
                 NO: 212 
               
               
                 SG213 
                 SEQ ID 
                 931 
                 MS4A1 
                 Of 4 domains which are expanded by the 
               
               
                   
                 NO: 213 
                   
                   
                 membrane, subfamily A, member 1 
               
               
                 SG214 
                 SEQ ID 
                 1380 
                 CR2 
                 Complement component receptor 
               
               
                   
                 NO: 214 
                   
                   
                 (3d/Epstein Barr&#39;s virus) 2 
               
               
                 SG215 
                 SEQ ID 
                 933 
                 CD22 
                 Antigen CD22 
               
               
                   
                 NO: 215 
               
               
                 SG216 
                 SEQ ID 
                 2208 
                 FCER2 
                 Low-affinity receptor II for the Fc fragment 
               
               
                   
                 NO: 216 
                   
                   
                 of IgE (CD23A) 
               
               
                 SG217 
                 SEQ ID 
                 934 
                 CD24 
                 Antigen CD24 (antigen of carcinoma of 
               
               
                   
                 NO: 217 
                   
                   
                 small lung cells of the grouping 4) 
               
               
                 SG218 
                 SEQ ID 
                 3559 
                 IL2RA 
                 interleukin 2 receptor, alpha 
               
               
                   
                 NO: 218 
               
               
                 SG219 
                 SEQ ID 
                 1803 
                 DPP4 
                 Dipeptidyl peptidase IV (CD26, protein 
               
               
                   
                 NO: 219 
                   
                   
                 which forms complexes with adenosine 
               
               
                   
                   
                   
                   
                 deaminase 2) 
               
               
                 SG220 
                 SEQ ID 
                 3688 
                 ITGB1 
                 Integrin, beta 1 (fibronectin receptor, beta 
               
               
                   
                 NO: 220 
                   
                   
                 polypeptide, antigen CD29 includes MDF2, 
               
               
                   
                   
                   
                   
                 MSK12) 
               
               
                 SG221 
                 SEQ ID 
                 943 
                 TNFRSF8 
                 Tumour necrosing factor receptor 
               
               
                   
                 NO: 221 
                   
                   
                 superfamily, member 8 
               
               
                 SG222 
                 SEQ ID 
                 945 
                 CD33 
                 Antigen CD33 (gp67) 
               
               
                   
                 NO: 222 
               
               
                 SG223 
                 SEQ ID 
                 947 
                 CD34 
                 Antigen CD34 
               
               
                   
                 NO: 223 
               
               
                 SG224 
                 SEQ ID 
                 948 
                 CD36 
                 Antigen CD36 (collagen type I receptor, 
               
               
                   
                 NO: 224 
                   
                   
                 thrombospondin receptor) 
               
               
                 SG225 
                 SEQ ID 
                 952 
                 CD38 
                 Antigen CD38 (p45) 
               
               
                   
                 NO: 225 
               
               
                 SG226 
                 SEQ ID 
                 958 
                 TNFRSF5 
                 Tumour necrosing factor receptor 
               
               
                   
                 NO: 226 
                   
                   
                 superfamily, member 5 
               
               
                 SG227 
                 SEQ ID 
                 6693 
                 SPN 
                 Sarcospan (Gene associated to the Kras 
               
               
                   
                 NO: 227 
                   
                   
                 oncogene) 
               
               
                 SG228 
                 SEQ ID 
                 960 
                 CD44 
                 Antigen CD44 (homing function and Indian 
               
               
                   
                 NO: 228 
                   
                   
                 blood group function) 
               
               
                 SG229 
                 SEQ ID 
                 960 
                 CD44v6 
                 Antigen CD44 (homing function and Indian 
               
               
                   
                 NO: 229 
                   
                   
                 blood group function) 
               
               
                 SG230 
                 SEQ ID 
                 5788 
                 PTPRCCD 
                 Protein thyrosine phosphatase, receptor 
               
               
                   
                 NO: 230 
                   
                   
                 type, C 
               
               
                 SG231 
                 SEQ ID 
                 961 
                 CD47 
                 Antigen CD47 (Antigen related to Rh, 
               
               
                   
                 NO: 231 
                   
                   
                 transducer of the signal associated to 
               
               
                   
                   
                   
                   
                 integrins) 
               
               
                 SG232 
                 SEQ ID 
                 3673 
                 ITGA2 
                 Integrin, alpha 2 (CD49B, alpha 2 subunit of 
               
               
                   
                 NO: 232 
                   
                   
                 receptor VLA-2) 
               
               
                 SG233 
                 SEQ ID 
                 3675 
                 ITGA3 
                 Integrin, alpha 3 (Antigen CD49C, alpha 
               
               
                   
                 NO: 233 
                   
                   
                 subunit 3 of receptor VLA-3) 
               
               
                 SG234 
                 SEQ ID 
                 3676 
                 ITGA4 
                 Integrin, alpha 4 (Antigen CD49D, alpha 
               
               
                   
                 NO: 234 
                   
                   
                 subunit 4 of receptor VLA-4) 
               
               
                 SG235 
                 SEQ ID 
                 3678 
                 ITGA5 
                 Integrin, alpha 5 (fibronectin receptor, alpha 
               
               
                   
                 NO: 235 
                   
                   
                 polypeptide) 
               
               
                 SG236 
                 SEQ ID 
                 3385 
                 ICAM3 
                 Intercellular adhesion molecule 3 
               
               
                   
                 NO: 236 
               
               
                 SG237 
                 SEQ ID 
                 1043 
                 CDW52 
                 Antigen CDW52 (antigen CAMPATH-1) 
               
               
                   
                 NO: 237 
               
               
                 SG238 
                 SEQ ID 
                 3383 
                 ICAM1 
                 Intercellular adhesion molecule 1 (CD54), 
               
               
                   
                 NO: 238 
                   
                   
                 human rhinovirus receptor 
               
               
                 SG239 
                 SEQ ID 
                 4684 
                 NCAM1 
                 Neural cell adhesion molecule 1 
               
               
                   
                 NO: 239 
               
               
                 SG240 
                 SEQ ID 
                 965 
                 CD58 
                 Antigen CD58 (antigen associated to the 
               
               
                   
                 NO: 240 
                   
                   
                 function of the lymphocytes 3) 
               
               
                 SG241 
                 SEQ ID 
                 966 
                 CD59 
                 Antigen CD59 p18-20 (antigen identified by 
               
               
                   
                 NO: 241 
                   
                   
                 the monoclonal antibodies 16.3A5, EJ16, 
               
               
                   
                   
                   
                   
                 EJ30, EL32 and G344) 
               
               
                 SG242 
                 SEQ ID 
                 6402 
                 SELL 
                 Selectin L (lymphocyte adhesion molecule 
               
               
                   
                 NO: 242 
                   
                   
                 1) 
               
               
                 SG243 
                 SEQ ID 
                 974 
                 CD79B 
                 Antigen CD79B (associated to beta 
               
               
                   
                 NO: 243 
                   
                   
                 immunoglobulins) 
               
               
                 SG244 
                 SEQ ID 
                 975 
                 CD81 
                 Antigen CD81 (target of the antiproliferative 
               
               
                   
                 NO: 244 
                   
                   
                 antibody 1) 
               
               
                 SG245 
                 SEQ ID 
                 3732 
                 KAI1 
                 Kangai 1 (suppression of tumorigenicity 6, 
               
               
                   
                 NO: 245 
                   
                   
                 prostate; antigen CD82 (leukocytes R2 
               
               
                   
                   
                   
                   
                 antigen, antigen detected by the 
               
               
                   
                   
                   
                   
                 monoclonal antibody IA4)) 
               
               
                 SG246 
                 SEQ ID 
                 9308 
                 CD83 
                 Antigen CD83 (activated B lymphocytes, 
               
               
                   
                 NO: 246 
                   
                   
                 immunoglobulins superfamily) 
               
               
                 SG247 
                 SEQ ID 
                 942 
                 CD86 
                 Antigen CD86 (ligand 2 of the antigen 
               
               
                   
                 NO: 247 
                   
                   
                 CD28, antigen B7-2) 
               
               
                 SG248 
                 SEQ ID 
                 355 
                 TNFRSF6 
                 Tumour necrosing factor receptor 
               
               
                   
                 NO: 248 
                   
                   
                 superfamily, member 6 
               
               
                 SG249 
                 SEQ ID 
                 356 
                 TNFSF6 
                 Tumour necrosing factor receptor 
               
               
                   
                 NO: 249 
                   
                   
                 superfamily (ligand), member 6 
               
               
                 SG250 
                 SEQ ID 
                 8140 
                 SLC7A5 
                 Solute-carrier family 7 (cationic amino acid 
               
               
                   
                 NO: 250 
                   
                   
                 carrier, y+ system), member 5 
               
               
                 SG251 
                 SEQ ID 
                 6382 
                 SDC1 
                 Sindecan 1 
               
               
                   
                 NO: 251 
               
               
                 SG252 
                 SEQ ID 
                 1019 
                 CDK4 
                 Cyclin-dependent kinase 4 
               
               
                   
                 NO: 252 
               
               
                 SG253 
                 SEQ ID 
                 6774 
                 STAT3 
                 Signal transducer and transcription activator 
               
               
                   
                 NO: 253 
                   
                   
                 3 (response factor in acute phase) 
               
               
                 SG254 
                 SEQ ID 
                 2268 
                 FGR 
                 Homologue to Gardner-Rasheed&#39;s feline 
               
               
                   
                 NO: 254 
                   
                   
                 viral sarcoma oncogene(v-fgr) 
               
               
                 SG255 
                 SEQ ID 
                 2353 
                 FOS 
                 Homologue to the murine viral 
               
               
                   
                 NO: 255 
                   
                   
                 osteosarcoma oncogene V-fos FBJ 
               
               
                 SG256 
                 SEQ ID 
                 898 
                 CCNE1 
                 Cyclin E1 
               
               
                   
                 NO: 256 
               
               
                 SG257 
                 SEQ ID 
                 978 
                 CDA 
                 Cytidine deaminase 
               
               
                   
                 NO: 257 
               
               
                 SG258 
                 SEQ ID 
                 9935 
                 MAFB 
                 Homologue to the fibrosarcoma 
               
               
                   
                 NO: 258 
                   
                   
                 oncogene (avian) musculoaponeurotic V- 
               
               
                   
                   
                   
                   
                 maf 
               
               
                 SG259 
                 SEQ ID 
                 4352 
                 MPL 
                 Oncogene of myeloproliferative leukemia 
               
               
                   
                 NO: 259 
                   
                   
                 virus 
               
               
                 SG260 
                 SEQ ID 
                 4609 
                 MYC 
                 Homologue to the avian myelocyomatosis 
               
               
                   
                 NO: 260 
                   
                   
                 viral oncogene V-myc 
               
               
                 SG261 
                 SEQ ID 
                 4602 
                 MYB 
                 Homologue to the avian myelocyomatosis 
               
               
                   
                 NO: 261 
                   
                   
                 viral oncogene V-myb 
               
               
                 SG262 
                 SEQ ID 
                 1159 
                 CKMT1 
                 Creatine kinase, mitochondrial 1 (ubicuous) 
               
               
                   
                 NO: 262 
               
               
                 SG263 
                 SEQ ID 
                 1387 
                 CREBBP 
                 CREB binding protein (Rubinstein-Taybi&#39;s 
               
               
                   
                 NO: 263 
                   
                   
                 syndrome) 
               
               
                 SG264 
                 SEQ ID 
                 1490 
                 CTGF 
                 Connective tissue growth factor 
               
               
                   
                 NO: 264 
               
               
                 SG265 
                 SEQ ID 
                 2833 
                 CXCR3 
                 Chemokene receptor 3 (motive C—X—C) 
               
               
                   
                 NO: 265 
               
               
                 SG266 
                 SEQ ID 
                 7852 
                 CXCR4 
                 Chemokene receptor 4 (motive C—X—C) 
               
               
                   
                 NO: 266 
                   
                   
                 (fusin) 
               
               
                 SG267 
                 SEQ ID 
                 8900 
                 CCNA1 
                 Cyclin A1 
               
               
                   
                 NO: 267 
               
               
                 SG268 
                 SEQ ID 
                 891 
                 CCNB1 
                 Cyclin B1 
               
               
                   
                 NO: 268 
               
               
                 SG269 
                 SEQ ID 
                 894 
                 CCND2 
                 Cyclin D2 
               
               
                   
                 NO: 269 
               
               
                 SG270 
                 SEQ ID 
                 1543 
                 CYP1A1 
                 Cytochrome P450, subfamily I (inducible by 
               
               
                   
                 NO: 270 
                   
                   
                 aromatic compounds), polypeptide 1 
               
               
                 SG271 
                 SEQ ID 
                 1565 
                 CYP2A6 
                 Cytochrome P450, subfamily IID (of 
               
               
                   
                 NO: 271 
                   
                   
                 metabolization of debrisokine, spartin, etc.), 
               
               
                   
                   
                   
                   
                 polypeptide 6 
               
               
                 SG272 
                 SEQ ID 
                 1603 
                 DAD-1 
                 Defender against cell death 1 
               
               
                   
                 NO: 272 
               
               
                 SG273 
                 SEQ ID 
                 8794 
                 TNFRSF10C 
                 Tumour necrosing factor receptor 
               
               
                   
                 NO: 273 
                   
                   
                 superfamily, member 10c, decoy without 
               
               
                   
                   
                   
                   
                 intracellular domain 
               
               
                 SG274 
                 SEQ ID 
                 7913 
                 DEK 
                 Oncogene DEK (which binds to DNA) 
               
               
                   
                 NO: 274 
               
               
                 SG275 
                 SEQ ID 
                 1633 
                 DCK 
                 Deoxycytidine kinase 
               
               
                   
                 NO: 275 
               
               
                 SG276 
                 SEQ ID 
                 1719 
                 DHFR 
                 Dihydrofolate reductase 
               
               
                   
                 NO: 276 
               
               
                 SG277 
                 SEQ ID 
                 6929 
                 TCF3 
                 Transcription factor 3 (immunoglobulin 
               
               
                   
                 NO: 277 
                   
                   
                 enhancer binding factors E2A E12/E47) 
               
               
                 SG278 
                 SEQ ID 
                 1869 
                 E2F1 
                 Transcription factor E2F 1 
               
               
                   
                 NO: 278 
               
               
                 SG279 
                 SEQ ID 
                 6929 
                 TCF3 
                 Transcription factor 3 (immunoglobulin 
               
               
                   
                 NO: 279 
                   
                   
                 enhancer binding factors E2A E12/E47) 
               
               
                 SG280 
                 SEQ ID 
                 56899 
                 EB-1 
                 Protein associated to E2a-Pbx1 
               
               
                   
                 NO: 280 
               
               
                 SG281 
                 SEQ ID 
                 1236 
                 CCR7 
                 Chemokene receptor 7 (motive C-C) 
               
               
                   
                 NO: 281 
               
               
                 SG282 
                 SEQ ID 
                 1880 
                 EBI2 
                 Gene induced by Epstein-Barr&#39;s 2 disease 
               
               
                   
                 NO: 282 
                   
                   
                 (receptor coupled to G proteins specific for 
               
               
                   
                   
                   
                   
                 lymphocytes) 
               
               
                 SG283 
                 SEQ ID 
                 4582 
                 MUC-1 
                 Mucin 1, transmembrane 
               
               
                   
                 NO: 283 
               
               
                 SG284 
                 SEQ ID 
                 2042 
                 EphA3 
                 EPHA3 
               
               
                   
                 NO: 284 
               
               
                 SG285 
                 SEQ ID 
                 2057 
                 EPOR 
                 Erythropoietin receptor 
               
               
                   
                 NO: 285 
               
               
                 SG286 
                 SEQ ID 
                 2067 
                 ERCC1 
                 Of repair of excision which 
               
               
                   
                 NO: 286 
                   
                   
                 intercomplements the deficiency in the 
               
               
                   
                   
                   
                   
                 repair of rodents, complementation group 1 
               
               
                   
                   
                   
                   
                 (includes the antisense overlapping 
               
               
                   
                   
                   
                   
                 sequence) 
               
               
                 SG287 
                 SEQ ID 
                 2068 
                 ERCC2 
                 Of repair of excision which 
               
               
                   
                 NO: 287 
                   
                   
                 intercomplements the deficiency in the 
               
               
                   
                   
                   
                   
                 repair of rodents, complementation group 2 
               
               
                   
                   
                   
                   
                 (xerodermia pigmentoso 2) 
               
               
                 SG288 
                 SEQ ID 
                 2071 
                 ERCC3 
                 Of repair of excision which 
               
               
                   
                 NO: 288 
                   
                   
                 intercomplements the deficiency in the 
               
               
                   
                   
                   
                   
                 repair of rodents, complementation group 3 
               
               
                   
                   
                   
                   
                 (complements group B of xerodermia 
               
               
                   
                   
                   
                   
                 pigmentoso) 
               
               
                 SG289 
                 SEQ ID 
                 2073 
                 ERCC5 
                 Of repair of excision which 
               
               
                   
                 NO: 289 
                   
                   
                 intercomplements the deficiency in the 
               
               
                   
                   
                   
                   
                 repair of rodents, complementation group 5 
               
               
                   
                   
                   
                   
                 (xerodermia pigmentoso, complementation 
               
               
                   
                   
                   
                   
                 group G (Cockayne&#39;s syndrome)) 
               
               
                 SG290 
                 SEQ ID 
                 2074 
                 ERCC6 
                 Of repair of excision which 
               
               
                   
                 NO: 290 
                   
                   
                 intercomplements the deficiency in the 
               
               
                   
                   
                   
                   
                 repair of rodents, complementation group 6 
               
               
                 SG291 
                 SEQ ID 
                 50624 
                 CUZD1 
                 With CUB domains and similar to the zone 
               
               
                   
                 NO: 291 
                   
                   
                 pellucida 1 
               
               
                 SG292 
                 SEQ ID 
                 2120 
                 ETV6 
                 Gene variant of ets 6 (TEL oncogene) 
               
               
                   
                 NO: 292 
               
               
                 SG293 
                 SEQ ID 
                 1977 
                 EIF4E 
                 Initiation factor of eukaryotic translation 4E 
               
               
                   
                 NO: 293 
               
               
                 SG294 
                 SEQ ID 
                 1984 
                 EIF5A 
                 Initiation factor of eukaryotic translation 5A 
               
               
                   
                 NO: 294 
               
               
                 SG295 
                 SEQ ID 
                 2146 
                 EZH2 
                 Zeste homologue enhancer ( Drosophila ) 2 
               
               
                   
                 NO: 295 
               
               
                 SG296 
                 SEQ ID 
                 8772 
                 FADD 
                 Associated to Fas (TNFRSF6) via 
               
               
                   
                 NO: 296 
                   
                   
                 apoptopic domain 
               
               
                 SG297 
                 SEQ ID 
                 5747 
                 PTK2 
                 Thyrosine kinase 2 protein 
               
               
                   
                 NO: 297 
               
               
                 SG298 
                 SEQ ID 
                 2195 
                 FAT 
                 Homologue to the FAT tumour suppressor 
               
               
                   
                 NO: 298 
                   
                   
                 ( Drosophila ) 
               
               
                 SG299 
                 SEQ ID 
                 2260 
                 FGFR1 
                 Fibroblast growth factor receptor 1 
               
               
                   
                 NO: 299 
                   
                   
                 (thyrosine kinase related to fms 2, Pfeiffer&#39;s 
               
               
                   
                   
                   
                   
                 syndrome) 
               
               
                 SG300 
                 SEQ ID 
                 2261 
                 FGFR3 
                 Fibroblast growth factor receptor 3 
               
               
                   
                 NO: 300 
                   
                   
                 (achondroplasia, thanatophoric dwarfism) 
               
               
                 SG301 
                 SEQ ID 
                 2272 
                 FHIT 
                 Fragile histidine triad gene 
               
               
                   
                 NO: 301 
               
               
                 SG302 
                 SEQ ID 
                 2322 
                 FLT3 
                 Thyrosine kinase related to Fms 3 
               
               
                   
                 NO: 302 
               
               
                 SG303 
                 SEQ ID 
                 2892 
                 GRIA3 
                 Glutamate receptor, ionotrophic, AMPA 3 
               
               
                   
                 NO: 303 
               
               
                 SG304 
                 SEQ ID 
                 2521 
                 FUS 
                 Fusion, derived from the malignant 
               
               
                   
                 NO: 304 
                   
                   
                 liposarcoma t(12;16) 
               
               
                 SG305 
                 SEQ ID 
                 1977 
                 EIF4E 
                 Initiation factor of eukaryotic translation 4E 
               
               
                   
                 NO: 305 
               
               
                 SG306 
                 SEQ ID 
                 6482 
                 SIAT4A 
                 Sialyltransferase 4A (beta-galactosidase 
               
               
                   
                 NO: 306 
                   
                   
                 alpha-2.3-Sialyltransferase) 
               
               
                 SG307 
                 SEQ ID 
                 1440 
                 CSF3 
                 Colony stimulating factor 3 (granulocyte) 
               
               
                   
                 NO: 307 
               
               
                 SG308 
                 SEQ ID 
                 1437 
                 CSF2 
                 Colony stimulating factor 2 (granulocyte- 
               
               
                   
                 NO: 308 
                   
                   
                 microphage) 
               
               
                 SG309 
                 SEQ ID 
                 2908 
                 NR3C1 
                 Subfamily of nuclear receptors 3, group C, 
               
               
                   
                 NO: 309 
                   
                   
                 member 1 
               
               
                 SG310 
                 SEQ ID 
                 2952 
                 GSTT1 
                 Glutathion S-transferase theta 1 
               
               
                   
                 NO: 310 
               
               
                 SG311 
                 SEQ ID 
                 3001 
                 GZMA 
                 Granzime A (granzime 1, serine stearase 
               
               
                   
                 NO: 311 
                   
                   
                 associated to cytotoxic T lymphocytes 3) 
               
               
                 SG312 
                 SEQ ID 
                 3301 
                 DNAJA1 
                 Homologue to DnaJ (Hsp40), subfamily A, 
               
               
                   
                 NO: 312 
                   
                   
                 member 1 
               
               
                 SG313 
                 SEQ ID 
                 3131 
                 HLF 
                 Hepatic leukemia factor 
               
               
                   
                 NO: 313 
               
               
                 SG314 
                 SEQ ID 
                 684 
                 BST2 
                 Antigen of bone marrow stroma cells 2 
               
               
                   
                 NO: 314 
               
               
                 SG315 
                 SEQ ID 
                 3205 
                 HOXA9 
                 Homeotic box A9 
               
               
                   
                 NO: 315 
               
               
                 SG316 
                 SEQ ID 
                 3195 
                 TLX1 
                 T lymphocyte leukemia, homeotic box 1 
               
               
                   
                 NO: 316 
               
               
                 SG317 
                 SEQ ID 
                 29128 
                 UHRF1 
                 similar to ubiquitine, which contains PHD 
               
               
                   
                 NO: 317 
                   
                   
                 domains and RING fingers, 1 
               
               
                 SG318 
                 SEQ ID 
                 8870 
                 IER3 
                 Immediate early response 3 
               
               
                   
                 NO: 318 
               
               
                 SG319 
                 SEQ ID 
                 3553 
                 IL1B 
                 Interleukin 1, beta 
               
               
                   
                 NO: 319 
               
               
                 SG320 
                 SEQ ID 
                 3558 
                 IL2 
                 Interleukin 2 
               
               
                   
                 NO: 320 
               
               
                 SG321 
                 SEQ ID 
                 3562 
                 IL3 
                 Interleukin 3 (multiple colony stimulating 
               
               
                   
                 NO: 321 
                   
                   
                 factor) 
               
               
                 SG322 
                 SEQ ID 
                 3569 
                 IL6 
                 Interleukin 6 (interferon, beta 2) 
               
               
                   
                 NO: 322 
               
               
                 SG323 
                 SEQ ID 
                 3570 
                 IL6R 
                 Interleukin receptor 6 
               
               
                   
                 NO: 323 
               
               
                 SG324 
                 SEQ ID 
                 3586 
                 IL10 
                 Interleukin 10 
               
               
                   
                 NO: 324 
               
               
                 SG325 
                 SEQ ID 
                 3600 
                 IL15 
                 Interleukin 15 
               
               
                   
                 NO: 325 
               
               
                 SG326 
                 SEQ ID 
                 3662 
                 IRF4 
                 Interferon regulating factor 4 
               
               
                   
                 NO: 326 
               
               
                 SG327 
                 SEQ ID 
                 3716 
                 JAK1 
                 Janus 2 kinase (a thyrosine kinase protein) 
               
               
                   
                 NO: 327 
               
               
                 SG328 
                 SEQ ID 
                 3717 
                 JAK2 
                 Janus 1 kinase (a thyrosine kinase protein) 
               
               
                   
                 NO: 328 
               
               
                 SG329 
                 SEQ ID 
                 4288 
                 MKI67 
                 Antigen identified by monoclonal antibody 
               
               
                   
                 NO: 329 
                   
                   
                 Ki-67 
               
               
                 SG330 
                 SEQ ID 
                 7520 
                 XRCC5 
                 Of repair of X rays which complements the 
               
               
                   
                 NO: 330 
                   
                   
                 defective repair in Chinese hamster cells 5 
               
               
                   
                   
                   
                   
                 (reconnection of breakages in the double 
               
               
                   
                   
                   
                   
                 helix; autoantigen Ku, 80 kDa) 
               
               
                 SG331 
                 SEQ ID 
                 3902 
                 LAG3 
                 Lymphocyte activation gene 3 
               
               
                   
                 NO: 331 
               
               
                 SG332 
                 SEQ ID 
                 3932 
                 LCK 
                 Lymphocyte specific protein thyrosine 
               
               
                   
                 NO: 332 
                   
                   
                 kinase 
               
               
                 SG333 
                 SEQ ID 
                 3936 
                 LCP1 
                 Cytosolic protein of lymphocytes 1 (L- 
               
               
                   
                 NO: 333 
                   
                   
                 plastin) 
               
               
                 SG334 
                 SEQ ID 
                 3953 
                 LEPR 
                 Leptin receptor 
               
               
                   
                 NO: 334 
               
               
                 SG335 
                 SEQ ID 
                 4005 
                 LMO2 
                 With LIM domains only 2 (similar to 
               
               
                   
                 NO: 335 
                   
                   
                 rombotin 1) 
               
               
                 SG336 
                 SEQ ID 
                 3976 
                 LIF 
                 Leukemia inhibiting factor (cholinergic 
               
               
                   
                 NO: 336 
                   
                   
                 differentiation factor) 
               
               
                 SG337 
                 SEQ ID 
                 9961 
                 LRP 
                 Main leap protein 
               
               
                   
                 NO: 337 
               
               
                 SG338 
                 SEQ ID 
                 4046 
                 LSP1 
                 Lymphocyte-specific protein 1 
               
               
                   
                 NO: 338 
               
               
                 SG339 
                 SEQ ID 
                 4066 
                 LYL1 
                 Sequence derived from lymphoblastic 
               
               
                   
                 NO: 339 
                   
                   
                 leukemia 1 
               
               
                 SG340 
                 SEQ ID 
                 4790 
                 NFKB1 
                 Nuclear factor of the enhancer of the gene 
               
               
                   
                 NO: 340 
                   
                   
                 of the light kappa polypeptide in B-1 
               
               
                   
                   
                   
                   
                 lymphocytes(p105) 
               
               
                 SG341 
                 SEQ ID 
                 4118 
                 MAL 
                 mal, T lymphocyte differentiation protein 
               
               
                   
                 NO: 341 
               
               
                 SG342 
                 SEQ ID 
                 4100 
                 MAGEA1 
                 Melanoma antigen, family A, 1 (directs the 
               
               
                   
                 NO: 342 
                   
                   
                 expression of antigen MZ2-E) 
               
               
                 SG343 
                 SEQ ID 
                 5602 
                 MAPK10 
                 Protein kinase activated by mitogens 10 
               
               
                   
                 NO: 343 
               
               
                 SG344 
                 SEQ ID 
                 2023 
                 MBP1 
                 Enolase 1, (alpha) 
               
               
                   
                 NO: 344 
               
               
                 SG345 
                 SEQ ID 
                 4170 
                 MCL1 
                 Leukemia sequence of myeloid cells 1 
               
               
                   
                 NO: 345 
                   
                   
                 (related to BCL2) 
               
               
                 SG346 
                 SEQ ID 
                 4193 
                 MDM2 
                 Human homologue of the double mouse 
               
               
                   
                 NO: 346 
                   
                   
                 diminuta 2; p53-binding protein 
               
               
                 SG347 
                 SEQ ID 
                 5243 
                 ABCB1 
                 ATP binding module, subfamily B 
               
               
                   
                 NO: 347 
                   
                   
                 (MDR/TAP), member 1 
               
               
                 SG348 
                 SEQ ID 
                 5244 
                 ABCB4 
                 ATP binding module, subfamily B 
               
               
                   
                 NO: 348 
                   
                   
                 (MDR/TAP), member 4 
               
               
                 SG349 
                 SEQ ID 
                 4221 
                 MEN1 
                 Multiple endocrine neoplasia I 
               
               
                   
                 NO: 349 
               
               
                 SG350 
                 SEQ ID 
                 4283 
                 CXCL9 
                 Chemokene ligand 9 (motive C—X—C) 
               
               
                   
                 NO: 350 
               
               
                 SG351 
                 SEQ ID 
                 4291 
                 MLF1 
                 Myeloid leukemia factor 1 
               
               
                   
                 NO: 351 
               
               
                 SG352 
                 SEQ ID 
                 4297 
                 MLL 
                 Myeloid/lymphoid leukemia or of mixed line 
               
               
                   
                 NO: 352 
                   
                   
                 (homologue to trithorax ( Drosophila )) 
               
               
                 SG353 
                 SEQ ID 
                 4318 
                 MMP9 
                 Metalloproteinase of matrix 9 (gelatinase B, 
               
               
                   
                 NO: 353 
                   
                   
                 92 kD gelatinase, 92 kD collagenase type IV) 
               
               
                 SG354 
                 SEQ ID 
                 4707 
                 NDUFB 
                 NADH dehydrogenase (ubiquinone) 1 beta 
               
               
                   
                 NO: 354 
                   
                   
                 subcomplex, 1 (7 kD, MNLL) 
               
               
                 SG355 
                 SEQ ID 
                 4353 
                 MPO 
                 Myeloperoxidase 
               
               
                   
                 NO: 355 
               
               
                 SG356 
                 SEQ ID 
                 8714 
                 ABCC3 
                 ATP binding module, subfamily C 
               
               
                   
                 NO: 356 
                   
                   
                 (CFTR/MRP), member 3 
               
               
                 SG357 
                 SEQ ID 
                 10057 
                 ABCC5 
                 ATP binding module, subfamily C 
               
               
                   
                 NO: 357 
                   
                   
                 (CFTR/MRP), member 5 
               
               
                 SG358 
                 SEQ ID 
                 4515 
                 MTCP1 
                 Proliferation of mature T-lymphocytes 1 
               
               
                   
                 NO: 358 
               
               
                 SG359 
                 SEQ ID 
                 4515 
                 MTCP1 
                 Proliferation of mature T-lymphocytes 1 
               
               
                   
                 NO: 359 
               
               
                 SG360 
                 SEQ ID 
                 4654 
                 MYOD1 
                 Myogenic factor 3 
               
               
                   
                 NO: 360 
               
               
                 SG361 
                 SEQ ID 
                 4599 
                 MX1 
                 Resistance to Myxovirus (flu) 1, homologue 
               
               
                   
                 NO: 361 
                   
                   
                 to the murine protein (protein inducible by 
               
               
                   
                   
                   
                   
                 interferon p78) 
               
               
                 SG362 
                 SEQ ID 
                 4814 
                 NINJ1 
                 Ninjurin 1 
               
               
                   
                 NO: 362 
               
               
                 SG363 
                 SEQ ID 
                 4869 
                 NPM1 
                 Nucleophosmin (nucleolar phosphoprotein 
               
               
                   
                 NO: 363 
                   
                   
                 B23, numatrin) 
               
               
                 SG364 
                 SEQ ID 
                 9235 
                 IL32 
                 Interleukin 32 
               
               
                   
                 NO: 364 
               
               
                 SG365 
                 SEQ ID 
                 4926 
                 NUMA1 
                 Nuclear protein of the myotic apparatus 1 
               
               
                   
                 NO: 365 
               
               
                 SG366 
                 SEQ ID 
                 5452 
                 POU2F2 
                 transcription factor with POU domain, of 
               
               
                   
                 NO: 366 
                   
                   
                 class 2, 2 
               
               
                 SG367 
                 SEQ ID 
                 5452 
                 POU2F2 
                 transcription factor with POU domain, of 
               
               
                   
                 NO: 367 
                   
                   
                 class 2, 2 
               
               
                 SG368 
                 SEQ ID 
                 4968 
                 OGGI 
                 8-oxoguanine-DNA-glycosilase 
               
               
                   
                 NO: 368 
               
               
                 SG369 
                 SEQ ID 
                 1030 
                 CDKN2B 
                 Cyclin-dependent kinase inhibitor 2B (p15, 
               
               
                   
                 NO: 369 
                   
                   
                 inhibits CDK4) 
               
               
                 SG370 
                 SEQ ID 
                 1029 
                 CDKN2A 
                 Cyclin-dependent kinase inhibitor 2A 
               
               
                   
                 NO: 370 
                   
                   
                 (melanoma, p16, inhibits CDK4) 
               
               
                 SG371 
                 SEQ ID 
                 1031 
                 CDKN2C 
                 Cyclin-dependent kinase inhibitor 2C (p18, 
               
               
                   
                 NO: 371 
                   
                   
                 inhibits CDK4) 
               
               
                 SG372 
                 SEQ ID 
                 1026 
                 CDKN1A 
                 Cyclin-dependent kinase inhibitor 1A (p21, 
               
               
                   
                 NO: 372 
                   
                   
                 Cip1) 
               
               
                 SG373 
                 SEQ ID 
                 1027 
                 CDKN1B 
                 Cyclin-dependent kinase inhibitor 1B (p27, 
               
               
                   
                 NO: 373 
                   
                   
                 Kip1) 
               
               
                 SG374 
                 SEQ ID 
                 8851 
                 CDK5R1 
                 Cyclin-dependent kinase 5, regulator 
               
               
                   
                 NO: 374 
                   
                   
                 subunit 1 (p35) 
               
               
                 SG375 
                 SEQ ID 
                 10210 
                 TOPORS 
                 Of binding to topoisomerase I, rich inc 
               
               
                   
                 NO: 375 
                   
                   
                 arginine/serine 
               
               
                 SG376 
                 SEQ ID 
                 991 
                 P55CDC 
                 CDC20 (cell division cycle 20,  S. cerevisiae , 
               
               
                   
                 NO: 376 
                   
                   
                 homologue) 
               
               
                 SG377 
                 SEQ ID 
                 1028 
                 CDKN1C 
                 Cyclin-dependent kinase inhibitor 1C (p57, 
               
               
                   
                 NO: 377 
                   
                   
                 Kip2) 
               
               
                 SG378 
                 SEQ ID 
                 7161 
                 TP73 
                 Tumour protein p73 
               
               
                   
                 NO: 378 
               
               
                 SG379 
                 SEQ ID 
                 5079 
                 PAX5 
                 Paired box gene 5 (specific activating 
               
               
                   
                 NO: 379 
                   
                   
                 protein of the B lymphocytes line) 
               
               
                 SG380 
                 SEQ ID 
                 5087 
                 PBX1 
                 Transcription factor of B 1 prelymphocytes 
               
               
                   
                 NO: 380 
                   
                   
                 leukemia 
               
               
                 SG381 
                 SEQ ID 
                 5090 
                 PBX3 
                 Transcription factor of B prelymphocytes 
               
               
                   
                 NO: 381 
                   
                   
                 leukemia B 3 
               
               
                 SG382 
                 SEQ ID 
                 5089 
                 ENPP1 
                 Ectonucleotide 
               
               
                   
                 NO: 382 
                   
                   
                 pyrophosphatase/phosphodiesterase 1 
               
               
                 SG383 
                 SEQ ID 
                 5167 
                 PCA1 
                 Ectonucleotide 
               
               
                   
                 NO: 383 
                   
                   
                 pyrophosphatase/phosphodiesterase 1 
               
               
                 SG384 
                 SEQ ID 
                 5111 
                 PCNA 
                 Nuclear antigen of proliferating cells 
               
               
                   
                 NO: 384 
               
               
                 SG385 
                 SEQ ID 
                 5159 
                 PDGFRB 
                 Platelet-derived growth factor receptor, beta 
               
               
                   
                 NO: 385 
                   
                   
                 polypeptide 
               
               
                 SG386 
                 SEQ ID 
                 5588 
                 PRKCQ 
                 kinase C protein, theta 
               
               
                   
                 NO: 386 
               
               
                 SG387 
                 SEQ ID 
                 5347 
                 PLK1 
                 Plasminogen activator, urokinase 
               
               
                   
                 NO: 387 
               
               
                 SG388 
                 SEQ ID 
                 5371 
                 PML 
                 Promielocytic leukemia 
               
               
                   
                 NO: 388 
               
               
                 SG389 
                 SEQ ID 
                 23532 
                 PRAME 
                 Antigen expressed preferentially in 
               
               
                   
                 NO: 389 
                   
                   
                 melanoma 
               
               
                 SG390 
                 SEQ ID 
                 5584 
                 PRKCI 
                 protein kinase C, iota 
               
               
                   
                 NO: 390 
               
               
                 SG391 
                 SEQ ID 
                 5728 
                 PTEN 
                 Phosphatase and homologue to tensin 
               
               
                   
                 NO: 391 
                   
                   
                 (mutated in multiple advanced cancers 1) 
               
               
                 SG392 
                 SEQ ID 
                 5742 
                 PTGS1 
                 prostaglandin-endoperoxide synthase 1 
               
               
                   
                 NO: 392 
                   
                   
                 (prostaglandin G/H synthase and 
               
               
                   
                   
                   
                   
                 cyclooxigenase) 
               
               
                 SG393 
                 SEQ ID 
                 5744 
                 PTHLH 
                 Hormone similar to the parathyroidal 
               
               
                   
                 NO: 393 
                   
                   
                 hormone 
               
               
                 SG394 
                 SEQ ID 
                 6688 
                 SPI1 
                 Oncogene of integration of provirus of focus 
               
               
                   
                 NO: 394 
                   
                   
                 forming virus in the spleen (SFFV) spi1 
               
               
                 SG395 
                 SEQ ID 
                 2185 
                 PTK2B 
                 Thyrosine kinase 2 beta protein 
               
               
                   
                 NO: 395 
               
               
                 SG396 
                 SEQ ID 
                 5889 
                 RAD51 
                 Homologue to RAD51 ( S. cerevisiae ) 
               
               
                   
                 NO: 396 
                   
                   
                 (homologue to RecA of  E. coli ) 
               
               
                 SG397 
                 SEQ ID 
                 5896 
                 RAG1 
                 Recombination activator gene 1 
               
               
                   
                 NO: 397 
               
               
                 SG398 
                 SEQ ID 
                 5914 
                 RARA 
                 Retinoic acid receptor, alpha 
               
               
                   
                 NO: 398 
               
               
                 SG399 
                 SEQ ID 
                 3845 
                 KRAS2 
                 Homologue to the viral oncogene of Kirsten 
               
               
                   
                 NO: 399 
                   
                   
                 2 V-Ki-ras2 rat sarcoma 
               
               
                 SG400 
                 SEQ ID 
                 5925 
                 RB1 
                 Retinoblastoma 1 (including osteosarcoma) 
               
               
                   
                 NO: 400 
               
               
                 SG401 
                 SEQ ID 
                 7422 
                 VEGF 
                 Vascular endothelial growth factor 
               
               
                   
                 NO: 401 
               
               
                 SG402 
                 SEQ ID 
                 7791 
                 ZYX 
                 Zyxin 
               
               
                   
                 NO: 402 
               
               
                 SG403 
                 SEQ ID 
                 940 
                 CD28 
                 Antigen CD28 (Tp44) 
               
               
                   
                 NO: 403 
               
               
                 SG404 
                 SEQ ID 
                 940 
                 CD28 
                 Antigen CD28 (Tp44) 
               
               
                   
                 NO: 404 
               
               
                 SG405 
                 SEQ ID 
                 1656 
                 RBBP4 
                 retinoblastoma 4 binding protein 
               
               
                   
                 NO: 405 
               
               
                 SG406 
                 SEQ ID 
                 1656 
                 DDX6 
                 Polypeptide with DEAD/H box (Asp-Glu- 
               
               
                   
                 NO: 406 
                   
                   
                 Ala-Asp/His) 6 (RNA helicase, 54 kD) 
               
               
                 SG407 
                 SEQ ID 
                 5928 
                 APEX 
                 APEX nuclease (multifunctional DNA repair 
               
               
                   
                 NO: 407 
                   
                   
                 enzyme DNA) 
               
               
                 SG408 
                 SEQ ID 
                 5977 
                 DPF2 
                 D4, family 2 with zinc fingers and double 
               
               
                   
                 NO: 408 
                   
                   
                 PHD 
               
               
                 SG409 
                 SEQ ID 
                 5996 
                 RGS1 
                 G protein signalling regulator G 1 
               
               
                   
                 NO: 409 
               
               
                 SG410 
                 SEQ ID 
                 3161 
                 HMMR 
                 Motility receptor mediated by hyaluronane 
               
               
                   
                 NO: 410 
                   
                   
                 (RHAMM) 
               
               
                 SG411 
                 SEQ ID 
                 6777 
                 STAT5B 
                 signal transducer and transcription activator 
               
               
                   
                 NO: 411 
                   
                   
                 5B 
               
               
                 SG412 
                 SEQ ID 
                 332 
                 BIRC5 
                 Which contains IAP repetitions of 
               
               
                   
                 NO: 412 
                   
                   
                 baculovirus 5 (survivin) 
               
               
                 SG413 
                 SEQ ID 
                 6886 
                 TAL1 
                 Acute lymphocytic leukemia of T 
               
               
                   
                 NO: 413 
                   
                   
                 lymphocytes 1 
               
               
                 SG414 
                 SEQ ID 
                 10482 
                 NXF1 
                 RNA exportation nuclear factor of RNA 1 
               
               
                   
                 NO: 414 
               
               
                 SG415 
                 SEQ ID 
                 8115 
                 TCL1A 
                 Leukemia/lymphoma of T 1A lymphocytes 
               
               
                   
                 NO: 415 
               
               
                 SG416 
                 SEQ ID 
                 6955 
                 TRA@ 
                 T locus alpha lymphocyte receptor 
               
               
                   
                 NO: 416 
               
               
                 SG417 
                 SEQ ID 
                   
                 TCR beta 
                 mRNA of the beta chain of the T 
               
               
                   
                 NO: 417 
                   
                   
                 lymphocyte receptor (TCRB) of  Homo   
               
               
                   
                   
                   
                   
                 
                   sapiens 
                 
               
               
                 SG418 
                 SEQ ID 
                 1791 
                 DNTT 
                 Deoxynucleotidyl transferase, terminal 
               
               
                   
                 NO: 418 
               
               
                 SG419 
                 SEQ ID 
                 7015 
                 TERT 
                 Inverse telomerase transcriptase 
               
               
                   
                 NO: 419 
               
               
                 SG420 
                 SEQ ID 
                 2066 
                 ERBB4 
                 Similar to the homologue to the viral 
               
               
                   
                 NO: 420 
                   
                   
                 oncogene of avian erythroblastic leukemia 
               
               
                   
                   
                   
                   
                 V-erb-a 4 
               
               
                 SG421 
                 SEQ ID 
                 2064 
                 ERBB2 
                 Homologue to the to the viral oncogene of 
               
               
                   
                 NO: 421 
                   
                   
                 avian erythroblastic leukemia V-erb-b2 2 
               
               
                   
                   
                   
                   
                 (homologue to the oncogene derived from 
               
               
                   
                   
                   
                   
                 neuro/glioblastoma) 
               
               
                 SG422 
                 SEQ ID 
                 1956 
                 EGFR 
                 Epidermal growth factor receptor 
               
               
                   
                 NO: 422 
                   
                   
                 (homologue to the viral oncogene of avian 
               
               
                   
                   
                   
                   
                 erythroblastic leukemia (v-erb-b)) 
               
               
                 SG423 
                 SEQ ID 
                 7066 
                 THPO 
                 Thrombopoietin (oncogene ligand of the 
               
               
                   
                 NO: 423 
                   
                   
                 myeloproliferative leukemia virus, growth 
               
               
                   
                   
                   
                   
                 factor and development of megakaryocytes) 
               
               
                 SG424 
                 SEQ ID 
                 7074 
                 TIAM1 
                 Invasion and metastasis of lymphoma of T 
               
               
                   
                 NO: 424 
                   
                   
                 lymphocytes 1 
               
               
                 SG425 
                 SEQ ID 
                 7083 
                 TK1 
                 Thymidine kinase 1, soluble 
               
               
                   
                 NO: 425 
               
               
                 SG426 
                 SEQ ID 
                 7132 
                 TNFRSF1A 
                 Tumour necrosing factor receptor 
               
               
                   
                 NO: 426 
                   
                   
                 superfamily, member 1A 
               
               
                 SG427 
                 SEQ ID 
                 7153 
                 TOP2A 
                 Topoisomerase (DNA) II alpha (170 kD) 
               
               
                   
                 NO: 427 
               
               
                 SG428 
                 SEQ ID 
                 1052 
                 CEBPD 
                 binding protein to CCAAT/enhancer 
               
               
                   
                 NO: 428 
                   
                   
                 (C/EBP), delta 
               
               
                 SG428 
                 SEQ ID 
                 9214 
                 FAIM3 
                 Apoptosis inhibitor molecule mediated by 
               
               
                   
                 NO: 428 
                   
                   
                 Fas 3 
               
               
                 SG429 
                 SEQ ID 
                 5358 
                 PLS3 
                 Plastin 3 (isoform T) 
               
               
                   
                 NO: 429 
               
               
                 SG430 
                 SEQ ID 
                 8717 
                 TRADD 
                 associated to TNFRSF1A via the cell death 
               
               
                   
                 NO: 430 
                   
                   
                 domain 
               
               
                 SG431 
                 SEQ ID 
                 8743 
                 TNFSF10 
                 Tumour necrosing factor superfamily 
               
               
                   
                 NO: 431 
                   
                   
                 (ligand) member 10 
               
               
                 SG432 
                 SEQ ID 
                 10131 
                 TRAP 1 
                 Thermal shock protein 75 
               
               
                   
                 NO: 432 
               
               
                 SG433 
                 SEQ ID 
                 7057 
                 THBS1 
                 Thrombospondin 1 
               
               
                   
                 NO: 433 
               
               
                 SG434 
                 SEQ ID 
                 7341 
                 SUMO1 
                 Homologue to the supressor of mif two 3 
               
               
                   
                 NO: 434 
                   
                   
                 SMT3 1 (yeast) 
               
               
                 SG435 
                 SEQ ID 
                 7405 
                 UVRAG 
                 Gene associated to UV radiation resistance 
               
               
                   
                 NO: 435 
               
               
                 SG436 
                 SEQ ID 
                 7441 
                 VPREB1 
                 Gene of B 1 prelymphocytes 
               
               
                   
                 NO: 436 
               
               
                 SG437 
                 SEQ ID 
                 51384 
                 WNT16 
                 family of MMTV integration site, Wingless- 
               
               
                   
                 NO: 437 
                   
                   
                 type, member 16 
               
               
                 SG438 
                 SEQ ID 
                 7490 
                 WT1 
                 Wilms tumour 1 
               
               
                   
                 NO: 438 
               
               
                 SG439 
                 SEQ ID 
                 7517 
                 XRCC3 
                 Of repair of X rays which complement the 
               
               
                   
                 NO: 439 
                   
                   
                 defective repair in Chinese hamster cells 3 
               
               
                 SG440 
                 SEQ ID 
                 896 
                 CCND3 
                 Cyclin D3 
               
               
                   
                 NO: 440 
               
               
                 SG441 
                 SEQ ID 
                 1017 
                 CDK2 
                 Cyclin-dependent kinase 2 
               
               
                   
                 NO: 441 
               
               
                 SG442 
                 SEQ ID 
                   
                 p14ARF 
                 Gene p14ARF from  Homo sapiens , 
               
               
                   
                 NO: 442 
                   
                   
                 promoter region, complete sequence 
               
               
                 SG443 
                 SEQ ID 
                 3070 
                 HELLS 
                 Helicase, specific for lymphoid cells 
               
               
                   
                 NO: 443 
               
               
                 SG444 
                 SEQ ID 
                 2624 
                 GATA2 
                 GATA 1-binding protein 2 
               
               
                   
                 NO: 444 
               
               
                 SG445 
                 SEQ ID 
                 2623 
                 GATA1 
                 GATA 1-binding protein (globin transcription 
               
               
                   
                 NO: 445 
                   
                   
                 factor 1) 
               
               
                 SG446 
                 SEQ ID 
                 8028 
                 MLLT10 
                 Myeloid/lymphoid leukemia or of mixed line 
               
               
                   
                 NO: 446 
                   
                   
                 (homologue to trithorax ( Drosophila )); 
               
               
                   
                   
                   
                   
                 translocated to 10 
               
               
                 SG447 
                 SEQ ID 
                 8301 
                 PICALM 
                 Clathrin assembly protein which binds to 
               
               
                   
                 NO: 447 
                   
                   
                 phosphatidylinositol 
               
               
                 SG448 
                 SEQ ID 
                 3815 
                 KIT 
                 Homologue to the viral oncogene of Hardy- 
               
               
                   
                 NO: 448 
                   
                   
                 Zuckerman&#39;s feline sarcoma 4 V-kit 
               
               
                 SG449 
                 SEQ ID 
                 3563 
                 IL3RA 
                 Interleukin 3 receptor, alpha (low affinity) 
               
               
                   
                 NO: 449 
               
               
                 SG450 
                 SEQ ID 
                 1050 
                 CEBPA 
                 binding protein to CCAAT/enhancer 
               
               
                   
                 NO: 450 
                   
                   
                 (C/EBP), alpha 
               
               
                 SG451 
                 SEQ ID 
                 3655 
                 ITGA6 
                 Integrin, alpha 6 
               
               
                   
                 NO: 451 
               
               
                 SG452 
                 SEQ ID 
                 84955 
                 CML66 
                 Tumour antigen of chronic myelogenous 
               
               
                   
                 NO: 452 
                   
                   
                 leukemia 66 
               
               
                 SG453 
                 SEQ ID 
                 7187 
                 TRAF3 
                 Factor associated to the TNF receptor 3 
               
               
                   
                 NO: 453 
               
               
                 SG454 
                 SEQ ID 
                 1612 
                 DAPK1 
                 Kinase protein associated to cell death 1 
               
               
                   
                 NO: 454 
               
               
                 SG455 
                 SEQ ID 
                 8788 
                 MAP3K12 
                 Homologue similar to Delta ( Drosophila ) 
               
               
                   
                 NO: 455 
               
               
                 SG456 
                 SEQ ID 
                 5591 
                 PRKDC 
                 Kinase protein, activated by DNA, catalytic 
               
               
                   
                 NO: 456 
                   
                   
                 polypeptide 
               
               
                 SG457 
                 SEQ ID 
                 1789 
                 DNMT3B 
                 (cytosine-5-)-methyltransferase 3 beta of 
               
               
                   
                 NO: 457 
                   
                   
                 DNA 
               
               
                 SG458 
                 SEQ ID 
                 2950 
                 GSTP1 
                 Glutathion S-transferase pi 
               
               
                   
                 NO: 458 
               
               
                 SG459 
                 SEQ ID 
                 3122 
                 HLA-DRA 
                 Complex greater than histocompatibility, 
               
               
                   
                 NO: 459 
                   
                   
                 class II, DR alpha 
               
               
                 SG460 
                 SEQ ID 
                 3206 
                 HOXA10 
                 Homeotic box A10 
               
               
                   
                 NO: 460 
               
               
                 SG461 
                 SEQ ID 
                 3394 
                 IRF8 
                 Binding protein to the agreed sequence of 
               
               
                   
                 NO: 461 
                   
                   
                 interferon 1 
               
               
                 SG462 
                 SEQ ID 
                 3398 
                 ID2 
                 DNA binding inhibitor 2, negative dominant 
               
               
                   
                 NO: 462 
                   
                   
                 helix-loops-helix protein 
               
               
                 SG463 
                 SEQ ID 
                 60 
                 ACTB 
                 Actin, beta 
               
               
                   
                 NO: 463 
               
               
                 SG464 
                 SEQ ID 
                 60 
                 ACTB 
                 Actin, beta 
               
               
                   
                 NO: 464 
               
               
                 SG465 
                 SEQ ID 
                 2868 
                 GRK4 
                 Kinase of receptor coupled to a protein G 4 
               
               
                   
                 NO: 465 
               
               
                 SG466 
                 SEQ ID 
                 2597 
                 GAPD 
                 Glyceraldehyde-3-phosphate 
               
               
                   
                 NO: 466 
                   
                   
                 dehydrogenase 
               
               
                 SG467 
                 SEQ ID 
                 2597 
                 GAPD 
                 Glyceraldehyde-3-phosphate 
               
               
                   
                 NO: 467 
                   
                   
                 dehydrogenase 
               
               
                 SG468 
                 SEQ ID 
                 6772 
                 STAT1 
                 Signal transducer and transcription activator 
               
               
                   
                 NO: 468 
                   
                   
                 1, 91 kDa 
               
               
                 SG469 
                 SEQ ID 
                   
                 18S rRNA 
                 Human rRNA gene 18S 
               
               
                   
                 NO: 469 
               
               
                 SG470 
                 SEQ ID 
                 7037 
                 TFRC 
                 Transferrin receptor (p90, CD71) 
               
               
                   
                 NO: 470 
               
               
                 SG471 
                 SEQ ID 
                   
                 28S rRNA 
                 Human ribosomal RNA gene 28S 
               
               
                   
                 NO: 471 
               
               
                 SG472 
                 SEQ ID 
                 6168 
                 RPL37A 
                 Ribosomal protein L37a 
               
               
                   
                 NO: 472 
               
               
                 SG473 
                 SEQ ID 
                 6171 
                 RPL41 
                 Ribosomal protein L41 
               
               
                   
                 NO: 473 
               
               
                 SG474 
                 SEQ ID 
                 3191 
                 HNRPL 
                 Heterogeneous nucler ribonucleoprotein L 
               
               
                   
                 NO: 474 
               
               
                 SG475 
                 SEQ ID 
                 3608 
                 ILF2 
                 Binding factor to the interleukin-2 enhancer, 
               
               
                   
                 NO: 475 
                   
                   
                 45 kD 
               
               
                 SG476 
                 SEQ ID 
                 8407 
                 TAGLN2 
                 Transgelin 2 
               
               
                   
                 NO: 476 
               
               
                 SG477 
                 SEQ ID 
                 824 
                 CAPN2 
                 Calpain 2, (m/II) major subunit 
               
               
                   
                 NO: 477 
               
               
                 SG478 
                 SEQ ID 
                 5686 
                 PSMA5 
                 Subunit of proteasome (prosome, 
               
               
                   
                 NO: 478 
                   
                   
                 macropain), type alpha, 5 
               
               
                 SG479 
                 SEQ ID 
                 27254 
                 PMM1 
                 Phosphomannomutase 1 
               
               
                   
                 NO: 479 
               
               
                 SG480 
                 SEQ ID 
                 8079 
                 MLF2 
                 Myeloid leukemia factor 2 
               
               
                   
                 NO: 480 
               
               
                 SG481 
                 SEQ ID 
                 5501 
                 PPP1CC 
                 Phosphatase protein 1, catalytic subunit, 
               
               
                   
                 NO: 481 
                   
                   
                 gamma isoform 
               
               
                 SG482 
                 SEQ ID 
                 22794 
                 CASC3 
                 Candidate for susceptibility to cancer 3 
               
               
                   
                 NO: 482 
               
               
                 SG483 
                 SEQ ID 
                 23164 
                 KIAA0864 
                 Protein KIAA0864 
               
               
                   
                 NO: 483 
               
               
                 SG484 
                 SEQ ID 
                 7296 
                 TXNRD1 
                 Thioredoxine reductase 1 
               
               
                   
                 NO: 484 
               
               
                 SG485 
                 SEQ ID 
                 5713 
                 PSMD7 
                 Subunit of proteasome (prosome, 
               
               
                   
                 NO: 485 
                   
                   
                 macropain) 26S, no-ATPase, 7 (homologue 
               
               
                   
                   
                   
                   
                 to Mov34) 
               
               
                 SG486 
                 SEQ ID 
                 8892 
                 EIF2B2 
                 initiation factor of eukaryotic translation 2B, 
               
               
                   
                 NO: 486 
                   
                   
                 subunit 2 (beta, 39 kD) 
               
               
                 SG487 
                 SEQ ID 
                 3105 
                 HLA-A 
                 Complex greater than histocompatibility, 
               
               
                   
                 NO: 487 
                   
                   
                 class I, A 
               
               
                 SG488 
                 SEQ ID 
                 4176 
                 MCM7 
                 Minichromosome maintenance deficient ( S. cerevisiae ) 7 
               
               
                   
                 NO: 488 
               
               
                 SG489 
                 SEQ ID 
                 8718 
                 TNFRSF25 
                 Tumour necrosing factor receptor 
               
               
                   
                 NO: 489 
                   
                   
                 superfamily, member 25 
               
               
                 SG490 
                 SEQ ID 
                 3958 
                 LGALS3 
                 Lectin, which binds to galactosides, soluble, 
               
               
                   
                 NO: 490 
                   
                   
                 3 (galectin 3) 
               
               
                 SG491 
                 SEQ ID 
                 311 
                 HLA-DPA1 
                 Complex greater than histocompatibility, 
               
               
                   
                 NO: 491 
                   
                   
                 class II, DP alpha 1 
               
               
                 SG492 
                 SEQ ID 
                 5328 
                 PLAU 
                 Plasminogen activator, urokinase 
               
               
                   
                 NO: 492 
               
               
                 SG493 
                 SEQ ID 
                 1281 
                 COL3A1 
                 Collagen, type III, alpha 1 (Ehlers-Danlos 
               
               
                   
                 NO: 493 
                   
                   
                 type IV syndrome, dominant autosomal) 
               
               
                 SG494 
                 SEQ ID 
                 287 
                 ANK2 
                 Ankyrin 2, neuronal 
               
               
                   
                 NO: 494 
               
               
                 SG495 
                 SEQ ID 
                 327657 
                 SERPINA9 
                 serine (or cysteine) proteinase inhibitor, 
               
               
                   
                 NO: 495 
                   
                   
                 clade A (alpha-1 antiproteinase, 
               
               
                   
                   
                   
                   
                 antitrypsin), member 9 
               
               
                 SG496 
                 SEQ ID 
                 10360 
                 NPM3 
                 Nucleophosmin/nucleoplasmin 3 
               
               
                   
                 NO: 496 
               
               
                 SG497 
                 SEQ ID 
                 1235 
                 CCR6 
                 Receptor 6 of chemokenes (motive C-C) 
               
               
                   
                 NO: 497 
               
               
                 SG498 
                 SEQ ID 
                 3055 
                 HCK 
                 Hematopoietic cell kinase 
               
               
                   
                 NO: 498 
               
               
                 SG499 
                 SEQ ID 
                 26354 
                 GNL3 
                 similar to guanine 3 nucleotide binding 
               
               
                   
                 NO: 499 
                   
                   
                 protein (nucleolar) 
               
               
                 SG500 
                 SEQ ID 
                 2885 
                 GRB2 
                 Protein bound to growth factor receptor 2 
               
               
                   
                 NO: 500 
               
               
                 SG501 
                 SEQ ID 
                 597 
                 BCL2A1 
                 protein related to BCL2 A1 
               
               
                   
                 NO: 501 
               
               
                 SG502 
                 SEQ ID 
                 1997 
                 ELF1 
                 Factor similar to E74 1 (transcription factor 
               
               
                   
                 NO: 502 
                   
                   
                 with ets domain) 
               
               
                 SG503 
                 SEQ ID 
                 1508 
                 CTSB 
                 Catepsin B 
               
               
                   
                 NO: 503 
               
               
                 SG504 
                 SEQ ID 
                 257144 
                 GCET2 
                 transcript expressed in the budding centre 2 
               
               
                   
                 NO: 504 
               
               
                 SG505 
                 SEQ ID 
                 2335 
                 FN1 
                 Fibronectin 1 
               
               
                   
                 NO: 505 
               
               
                 SG506 
                 SEQ ID 
                 5133 
                 PDCD1 
                 Programme cell death 1 
               
               
                   
                 NO: 506 
               
               
                 SG507 
                 SEQ ID 
                 3125 
                 HLA-DRB3 
                 Complex greater than histocompatibility, 
               
               
                   
                 NO: 507 
                   
                   
                 class II, DR beta 3 
               
               
                 SG508 
                 SEQ ID 
                 3117 
                 HLA-DQA1 
                 Complex greater than histocompatibility, 
               
               
                   
                 NO: 508 
                   
                   
                 class II, DQ alpha 1 
               
               
                 SG509 
                 SEQ ID 
                 257144 
                 GCET2 
                 transcript expressed in the budding centre 
               
               
                   
                 NO: 509 
                   
                   
                 germinal 2 
               
               
                 SG510 
                 SEQ ID 
                 327657 
                 SERPINA9 
                 serine (or cysteine) proteinase inhibitor, 
               
               
                   
                 NO: 510 
                   
                   
                 clade A (alpha-1 antiproteinase, 
               
               
                   
                   
                   
                   
                 antitrypsin), member 9 
               
               
                 SG511 
                 SEQ ID 
                 1033 
                 CDKN3 
                 Cyclin dependent kinases 3 (phosphatase 
               
               
                   
                 NO: 511 
                   
                   
                 of dual specificity associated CDK2) 
               
               
                 SG512 
                 SEQ ID 
                 1997 
                 ELF1 
                 Factor similar to E74 1 (transcription factor 
               
               
                   
                 NO: 512 
                   
                   
                 with ets domain) 
               
               
                 SG513 
                 SEQ ID 
                 1509 
                 CATSD 
                 Catepsin D (liposomal aspartylprotease) 
               
               
                   
                 NO: 513 
               
               
                 SG514 
                 SEQ ID 
                 3315 
                 HSPB1 
                 Thermal shock protein of 27 kD 1 
               
               
                   
                 NO: 514 
               
               
                 SG515 
                 SEQ ID 
                 87 
                 ACTN1 
                 Actinin, alpha 1 
               
               
                   
                 NO: 515 
               
               
                 SG516 
                 SEQ ID 
                 654 
                 BMP6 
                 Morphogenetic bone protein 6 
               
               
                   
                 NO: 516 
               
               
                 SG517 
                 SEQ ID 
                 9780 
                 FAM38A 
                 family with similarity of sequence 38, member A 
               
               
                   
                 NO: 517 
               
               
                 SG518 
                 SEQ ID 
                 962 
                 CD48 
                 Antigen CD48 (membrane protein of B 
               
               
                   
                 NO: 518 
                   
                   
                 lymphocytes) 
               
               
                 SG519 
                 SEQ ID 
                 3566 
                 IL4R 
                 Interleukin 4 receptor 
               
               
                   
                 NO: 519 
               
               
                 SG520 
                 SEQ ID 
                 1821 
                 DRP2 
                 Dystrophin related protein 2 
               
               
                   
                 NO: 520 
               
               
                 SG521 
                 SEQ ID 
                 3726 
                 JUNB 
                 Jun B Proto-oncogene 
               
               
                   
                 NO: 521 
               
               
                 SG522 
                 SEQ ID 
                 6279 
                 S100A8 
                 Calcium-binding protein S100 A8 
               
               
                   
                 NO: 522 
                   
                   
                 (calgranuline A) 
               
               
                 SG523 
                 SEQ ID 
                 10320 
                 ZNFN1A1 
                 Protein with zinc fingers, subfamily 1A, 1 
               
               
                   
                 NO: 523 
                   
                   
                 (lkaros) 
               
               
                 SG524 
                 SEQ ID 
                 10461 
                 MERTK 
                 Thyrosine kinase of the C-mer proto- 
               
               
                   
                 NO: 524 
                   
                   
                 oncogene 
               
               
                 SG525 
                 SEQ ID 
                 51621 
                 KLF13 
                 Factor similar to that of Kruppel 13 
               
               
                   
                 NO: 525 
               
               
                 SG526 
                 SEQ ID 
                 865 
                 CBFB 
                 Nucleus-binding factor, beta subunit 
               
               
                   
                 NO: 526 
               
               
                 SG527 
                 SEQ ID 
                 1051 
                 CEBPB 
                 binding protein to CCAAT/enhancer 
               
               
                   
                 NO: 527 
                   
                   
                 (C/EBP), beta 
               
               
                 SG529 
                 SEQ ID 
                 7024 
                 TFCP2 
                 Transcription factor CP2 
               
               
                   
                 NO: 529 
               
               
                 SG530 
                 SEQ ID 
                 1385 
                 CREB1 
                 CAMP response element binding protein 
               
               
                   
                 NO: 530 
               
               
                 SG531 
                 SEQ ID 
                 4782 
                 NFIC 
                 I/C nuclear factor (CCAAT binding factor 
               
               
                   
                 NO: 531 
                   
                   
                 transcription factor) 
               
               
                 SG532 
                 SEQ ID 
                 2553 
                 GABPB2 
                 Transcription factor of the protein which 
               
               
                   
                 NO: 532 
                   
                   
                 binds to GA, beta 2 subunit (47 kD) 
               
               
                 SG533 
                 SEQ ID 
                 1958 
                 EGR1 
                 Early growth response 1 
               
               
                   
                 NO: 533 
               
               
                 SG534 
                 SEQ ID 
                 10661 
                 KLF1 
                 Factor similar to that of Kruppel 1 
               
               
                   
                 NO: 534 
                   
                   
                 (erythroid) 
               
               
                 SG535 
                 SEQ ID 
                 1997 
                 ELF1 
                 Factor similar to E74 1 (transcription factor 
               
               
                   
                 NO: 535 
                   
                   
                 with ets domain) 
               
               
                 SG536 
                 SEQ ID 
                 2113 
                 ETS1 
                 homologue to the E26 oncogene of 
               
               
                   
                 NO: 536 
                   
                   
                 erythroblastosis virus v-ets 1 (avian) 
               
               
                 SG537 
                 SEQ ID 
                 2114 
                 ETS2 
                 homologue to the E26 oncogene of 
               
               
                   
                 NO: 537 
                   
                   
                 erythroblastosis virus v-ets 2 (avian) 
               
               
                 SG538 
                 SEQ ID 
                 2313 
                 FLI1 
                 Integration of Friend 1 leukemia virus 
               
               
                   
                 NO: 538 
               
               
                 SG539 
                 SEQ ID 
                 2625 
                 GATA3 
                 GATA 3 binding protein 
               
               
                   
                 NO: 539 
               
               
                 SG540 
                 SEQ ID 
                 862 
                 CBFA2T1 
                 Nucleus binding factor, runt domain, alpha 
               
               
                   
                 NO: 540 
                   
                   
                 2 subunit; translocated to 1; related to cyclin D 
               
               
                 SG541 
                 SEQ ID 
                 3091 
                 HIF1A 
                 Factor inducible by hypoxia 1, alpha subunit 
               
               
                   
                 NO: 541 
                   
                   
                 (basic transcription factor of helix-loops- 
               
               
                   
                   
                   
                   
                 helix) 
               
               
                 SG542 
                 SEQ ID 
                 6927 
                 TCF1 
                 Transcription factor 1, hepatic; LF-B1, 
               
               
                   
                 NO: 542 
                   
                   
                 hepatic nuclear factor (HNF1), proximal 
               
               
                   
                   
                   
                   
                 factor of albumin 
               
               
                 SG543 
                 SEQ ID 
                 3234 
                 HOXD8 
                 Homeotic box D8 
               
               
                   
                 NO: 543 
               
               
                 SG544 
                 SEQ ID 
                 3235 
                 HOXD9 
                 Homeotic box D9 
               
               
                   
                 NO: 544 
               
               
                 SG545 
                 SEQ ID 
                 9935 
                 MAFB 
                 Family of the oncogene of 
               
               
                   
                 NO: 545 
                   
                   
                 musculoaponeurotic fibrosarcoma (avian) 
               
               
                   
                   
                   
                   
                 V-maf 
               
               
                 SG546 
                 SEQ ID 
                 7975 
                 MAFK 
                 Family of the oncogene of 
               
               
                   
                 NO: 546 
                   
                   
                 musculoaponeurotic fibrosarcoma (avian) 
               
               
                   
                   
                   
                   
                 V-maf, protein K 
               
               
                 SG547 
                 SEQ ID 
                 8721 
                 EDF1 
                 factor related to edothelialdifferentiation 1 
               
               
                   
                 NO: 547 
               
               
                 SG548 
                 SEQ ID 
                 2000 
                 ELF4 
                 Factor similar to E74 4 (transcription factor 
               
               
                   
                 NO: 548 
                   
                   
                 with ets domain) 
               
               
                 SG549 
                 SEQ ID 
                 7593 
                 ZNF42 
                 Protein with zinc fingers 142 (clone pHZ-49) 
               
               
                   
                 NO: 549 
               
               
                 SG550 
                 SEQ ID 
                 4763 
                 NF1 
                 neurofibromin 1 
               
               
                   
                 NO: 550 
               
               
                 SG551 
                 SEQ ID 
                 4772 
                 NFATC1 
                 Nuclear factor of activated T-lymphocytes, 
               
               
                   
                 NO: 551 
                   
                   
                 cytoplasmic, calcineurin 1-dependent 
               
               
                 SG552 
                 SEQ ID 
                 5080 
                 PAX6 
                 Paired box gene 6 (aniridia, keratitis) 
               
               
                   
                 NO: 552 
               
               
                 SG553 
                 SEQ ID 
                 7849 
                 PAX8 
                 Paired box gene 8 
               
               
                   
                 NO: 553 
               
               
                 SG554 
                 SEQ ID 
                 57026 
                 PLP 
                 Pyridoxal (pyridoxine, vitamin B6) 
               
               
                   
                 NO: 554 
                   
                   
                 phosphatase 
               
               
                 SG555 
                 SEQ ID 
                 2274 
                 PLZF 
                 With four LIM domains and average 2 
               
               
                   
                 NO: 555 
               
               
                 SG556 
                 SEQ ID 
                 5950 
                 RBP4 
                 Retinol 4-binding protein, plasma 
               
               
                   
                 NO: 556 
               
               
                 SG557 
                 SEQ ID 
                 6095 
                 RORA 
                 Orphan receptor related to RAR A 
               
               
                   
                 NO: 557 
               
               
                 SG558 
                 SEQ ID 
                 6667 
                 SP1 
                 Transcription factor Sp1 
               
               
                   
                 NO: 558 
               
               
                 SG559 
                 SEQ ID 
                 6772 
                 STAT1 
                 Signal transducer and transcription activator 
               
               
                   
                 NO: 559 
                   
                   
                 1, 91 kDa 
               
               
                 SG560 
                 SEQ ID 
                 6908 
                 TBP 
                 TATA box-binding protein 
               
               
                   
                 NO: 560 
               
               
                 SG561 
                 SEQ ID 
                 6932 
                 TCF7 
                 Transcription factor 7 (T lymphocyte 
               
               
                   
                 NO: 561 
                   
                   
                 specific, box HMG) 
               
               
                 SG562 
                 SEQ ID 
                 51513 
                 ETV7 
                 Gene variant of ets 7 (oncogene TEL2) 
               
               
                   
                 NO: 562 
               
               
                 SG563 
                 SEQ ID 
                 7535 
                 ZAP70 
                 Zeta chain associated kinase protein (TCR) 
               
               
                   
                 NO: 563 
                   
                   
                 (70 kD) 
               
               
                   
               
             
          
         
       
     
         [0145]    From among these genes, four of them (ACTB, GAPD, 18S rRNA and 28S rRNA), do not have a special relation with neoplasias and were initially included in the microarray because, for a long time, it was believed that their expression remained constant and they were used when normalizing the microarray data: they are the type of genes alluded to when we speak of “constitutive” genes at other points in the specification. At present, it is not thought that there is a gene whose expression remains constant in any circumstance, for which reason, in the present study, the genes ACTB, GAPD, 18S rRNA and 28S rRNA have received the same treatment as the other genes of the microarray, except for the fact that the first two of them have been used as integrity controls, as described further on. 
         [0146]    In Table 1 it can be observed that there are genes which are represented by more than one oligonucleotide. This is the case because the existence of two or more probes per gene can be used to measure the integrity of the synthesized cRNA. The genes for which more than one oligonucleotide have been designed to act as probe, each one of which hybridizes with a different sequence, are indicated below in Table 2. 
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 Genes represented by more than one oligonucleotide as probe 
               
             
          
           
               
                 Usual abbreviation 
                   
                   
                   
               
               
                 of the gene 
                 Probe1 
                 Probe2 
                 Probe3 
               
               
                   
               
               
                 ABL1 
                 SG10 
                 SG180 
                   
               
               
                 BCR 
                 SG169 
                 SG170 
                   
               
               
                 CBFB 
                 SG189 
                 SG526 
                   
               
               
                 CD28 
                 SG403 
                 SG404 
                   
               
               
                 EIF4E 
                 SG293 
                 SG305 
                   
               
               
                 ELF1 
                 SG512 
                 SG535 
                 SG502 
               
               
                 ETS2 
                 SG95 
                 SG537 
                   
               
               
                 GCET2 
                 SG504 
                 SG509 
                   
               
               
                 MAFB 
                 SG258 
                 SG545 
                   
               
               
                 MTCP1 
                 SG358 
                 SG359 
                   
               
               
                 POU2F2 
                 SG366 
                 SG367 
                   
               
               
                 RGS1 
                 SG56 
                 SG409 
                   
               
               
                 S100A2 
                 SG35 
                 SG71 
                   
               
               
                 SNRPB 
                 SG142 
                 SG143 
                   
               
               
                 STAT1 
                 SG77 
                 SG559 
                 SG468 
               
               
                 TIA-2 
                 SG7 
                 SG73 
                   
               
               
                 TAGLN2 
                 SG24 
                 SG476 
                   
               
               
                 TCF3 
                 SG277 
                 SG279 
                   
               
               
                 XRCC5 
                 SG32 
                 SG330 
                   
               
               
                 ZYX 
                 SG97 
                 SG402 
                   
               
               
                 CD44 
                 SG228 
                 SG229 
                   
               
               
                 ACTB 
                 SG463 
                 SG464 
                   
               
               
                 GAPD 
                 SG464 
                 SG467 
               
               
                   
               
             
          
         
       
     
       Establishment of Control Probes 
       [0147]    To decrease the variability, a large number of controls were included in each microarray. These controls suppose an objective measurement on the process quality, and therefore, of the quality of the data obtained. They are of several types and origins: 
         [0148]    a) Probes Used as Integrity Controls 
         [0149]    These probes were 2 pairs of oligonucleotides complementary to ends 5′ and 3′ of the β-actin genes (probes code SG463 and SG464) and glyceraldehyde-3-phosphate dehydrogenase (probes code SG466 and SG467). The ratio between the intensities of the probe located at end 3′ and 5′ makes it possible to check the quality of the starting RNA and the functioning of the labelling reaction. The details on these oligonucleotides appear in Table 3. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 Oligonucleotides used as integrity controls 
               
             
          
           
               
                 Oligo- 
                   
                   
                 Gene 
                 GenID 
               
               
                 nucleotide 
                 SEQ ID NO: 
                 Source gene 
                 Abbreviation 
                 No. 
               
               
                   
               
               
                 SG463 
                 SEQ ID 
                 β-actin 
                 ACTB 
                  60 
               
               
                   
                 NO: 463 
                   
                   
                   
               
               
                 SG464 
                 SEQ ID 
                 β-actin 
                 ACTB 
                  60 
               
               
                   
                 NO: 464 
                   
                   
                   
               
               
                 SG466 
                 SEQ ID 
                 Glyceraldehyde-3- 
                 GAPD 
                 2597 
               
               
                   
                   
                 phosphate 
                   
                   
               
               
                   
                 NO: 466 
                 dehydrogenase 
                   
                   
               
               
                 SG467 
                 SEQ ID 
                 Glyceraldehyde-3- 
                 GAPD 
                 2597 
               
               
                   
                   
                 phosphate 
                   
                   
               
               
                   
                 NO: 467 
                 dehydrogenase 
               
               
                   
               
             
          
         
       
     
       b) Probes Used as Negative Controls 
       [0150]    These probes are largely formed by a group of oligonucleotides of 50 nucleotides (50-mer) which are not complementary to any known human sequence. For them, the BLAST tool was applied to these probes and it was observed that they did not hybridize with any human sequence. They are identified with codes SC1 (SEQ ID NO:564), SC2 (SEQ ID NO:565), SC3 (SEQ ID NO:566), SC4 (SEQ ID NO:567), SC5 (SEQ ID NO:568), SC6 (SEQ ID NO:569) and SC7 (SEQ ID NO:570) and oligonucleotides SCN1 (SEQ ID NO:571), SCN5 (SEQ ID NO:575), SCN7 (SEQ ID NO:577) and SCN10 (SEQ ID NO:580) are also used as negative controls. They are used to determine the optimum conditions of hybridization, washing and developing of the chips or microarrays. The appearance of a signal associated to them indicates the existence of non-specific hybridization. 
         [0151]    c) Exogenous Probes Used as Internal Positive Controls: “Spiked Controls” 
         [0152]    “Spiked controls” are synthetic oligonucleotides whose sequence coincides with a fragment of a transcript of a non-human gene or of any other sequence of nucleotides of low homology with transcripts of human genes which is polyadenylated at 3′, which is used as positive control, in the determination of the process quality, in the normalization of data and for the establishment of the linear range of the process (Benes V et al., 2003). To do this, the transcripts or corresponding polyadenylated sequences are added to the total starting RNA before starting the labelling process, and therefore, they suffer the same reactions (labelling, hybridization and developing) as the total 
         [0153]    RNA of the samples. 
         [0154]    7 “Spiked controls” are used. To ensure low homology with human genes 5 transcripts of  Bacillus subtilis  genes (dap, thr, trp, phe and lys) and 2 transcripts of genes of the Sharkav virus are used, frequently referred to as “Plum poxvirus” (Sppv), which is a plant virus. The details on these oligonucleotides are shown below in Table 4. The ATCC (American Type Culture Collection) numbers which appear after the name of the source genes refer to the identification number in the ATCC of  E. coli  strains containing recombinant plasmids which contain the sequence of the genes from which the transcripts added to the RNA are obtained and which were also used for the design of the sequences of the corresponding oligonucleotides bound to the microarray. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 4 
               
             
             
               
                   
               
               
                 Oligonucleotides used as “Spiked Controls” 
               
             
          
           
               
                   
                   
                   
                   
                   
                 Concentration 
               
               
                   
                   
                   
                   
                 Transcript 
                 (pM) in the 
               
               
                 Oligo- 
                   
                   
                 Gene Bank 
                 size 
                 “spiked controls” 
               
               
                 nucleotides 
                 SEQ ID NO: 
                 Source gene 
                 code 
                 (nt) 
                 solution 
               
               
                   
               
             
          
           
               
                 SSPC1 
                 SEQ ID 
                 Dap 
                 L38424 
                 1820 
                 2000 
               
               
                   
                 NO: 584 
                 (ATCC no. 87486) 
                   
                   
                   
               
               
                 SSPC2 
                 SEQ ID 
                 Lys 
                 X17013 
                 1000 
                 1250 
               
               
                   
                 NO: 585 
                 (ATCC no. 87482) 
                   
                   
                   
               
               
                 SSPC3 
                 SEQ ID 
                 Thr 
                 X04603 
                 1980 
                 5 
               
               
                   
                 NO: 586 
                 (ATCC no. 87484) 
                   
                   
                   
               
               
                 SSPC4 
                 SEQ ID 
                 Plum pox virus, 
                 AF401296 
                   
                 100 
               
               
                   
                 NO: 587 
                 isolated PENN2 (Sppv1) 
                   
                   
                   
               
               
                 SSPC5 
                 SEQ ID 
                 Plum pox potyvirus, 
                 X57975 
                   
                 750 
               
               
                   
                 NO: 588 
                 mRNA coated protein (Sppv2) 
                   
                   
                   
               
               
                 SSPC6 
                 SEQ ID 
                 Phe 
                 M24537 
                 1320 
                 1000 
               
               
                   
                 NO: 589 
                 (ATCC no. 87483) 
                   
                   
                   
               
               
                 SSPC7 
                 SEQ ID 
                 Trp 
                 K01391 
                 2500 
                 500 
               
               
                   
                 NO: 590 
                 (ATCC no. 87485) 
               
               
                   
               
             
          
         
       
     
         [0155]    c. 1.: Preparation of the 5 “Spiked controls” of  Bacillus subtilis    
         [0156]    The  E. coli  bacteria with the recombinant plasmids were acquired from ATCC (Rockville, Md. USA) The plasmids (pBluescript II-KS) contained the cloned cDNA of a  Bacillus subtilis  gene, with cut-off sites for the NotI enzymes at end 5′ and BamHI at end 3′ and a poly extension (dA) prior to the cut-off site for BamHI. 
         [0157]    After reconstituting and allowing the cells to grow during the night at 37° C. in LB+Ampicillin medium, the plasmid was obtained with the Midipreps kit (Jetstar) following the manufacturer&#39;s recommendations. 10 μg of each one of the plasmids was linearized by digestion with 30 U of NotI restriction enzyme, in the presence of 1XNE3 and 1XBSA buffer during 3 hours at 37° C. The linearized plasmids were subjected to extraction with phenol:chloroform:isoamilic alcohol (Ambion), precipitation with 0.1 vol of 3M sodium acetate (Sigma) and 2.5 vol of 100% Ethanol and elimination of salts with 80% Ethanol, following the aforementioned protocol. The DNA obtained was resuspended in 10 μl of RNase-free water. 
         [0158]    Next, the transcripts with sense were synthesized with an in vitro transcription reaction (I.V.T) from 1 μg of plasmid linearized using the MegaScript T3 kit (Ambion) and following the manufacturer&#39;s recommendations. The plasmids obtained were purified with the RNeasy Total RNA Isolation Kit (QIAGEN), following the manufacturer&#39;s recommendations. 
         [0159]    The quantification, determination of the purity, quality and size of the transcripts obtained were performed following the same methods which are described below for the total RNA. 
         [0160]    c.2. Preparation of the 2 “Spiked Controls” which Represent SPPV Genes 
         [0161]    The recombinant plasmids (Progenika Biopharma) contained the cloned 
         [0162]    cDNA of the two sppvl and sspv2 genes inserted between two PvuII and PstI restriction sites. End 3′ of each insert contains a polyadenylation extension. 
         [0163]    JM109 cells were transformed with the plasmids which contained the transcripts. The cells were left to grow in plates with LB+Ampicillin medium at 37° C., the colonies with the transferred cells were selected and they were grown in LB+AMP liquid medium. 
         [0164]    The recovery of the plasmids was performed with the Midipreps Plasmid Purification kit (Qiagen), following the manufacturer&#39;s recommendations. 10 μg of each plasmid was linearized with 30 U of the PvuII restriction enzyme. The insert was extracted with phenol:chloroform:isoamilic alcohol (Ambion), precipitation with 0.1 volumes of 7.5 M sodium acetate and 2.5 volumes of 100% ethanol. The salts were eliminated by two washings with 80% ethanol. The DNA obtained was resuspended in 10 μl of Rnase-free water. 
         [0165]    Next, the transcripts with sense were synthesized with 1 μg of plasmid linearized using the T7 MegaScript kit (Ambion) and following the manufacturer&#39;s recommendations. The product of the reaction was cleaned with the RNeasy Total RNA Isolation Kit (Qiagen). 
         [0166]    The quantification, measuring of the purity of the transcripts obtained and verification of their size were then performed 
         [0167]    A solution of “Spiked controls” was prepared from the transcripts obtained with different concentrations of each one of those “spiked” (see Table 3), so that they covered the whole range of intensities of the “scanner” reader system (values of intensity which go from 0 to 65,535 in arbitrary units). This solution was added in the same quantity to 5□ μg of total starting RNA from each sample before starting the process. 
         [0168]    c.3. Design of Probes Representative of Each One of the Transcripts: 
         [0169]    So that the behaviour of the probes was as similar as possible to the probes designed for the genes to be studied, with the Oligo 6.0 programme (M.B.I), those sequences were selected for each “Spiked control” which complied with the same requirements established for the probes of the genes represented (length, GC content, “sense” strand and distance to end 3′) and which did not form stable loops (energy less than −7 Kcal/mol). The BLAST tool was applied to the sequences which complied with those requirements and that with less homology with human sequences was chosen. 
         [0170]    After depositing and immobilizing the probes corresponding to the “Spiked controls” on the glass, it was verified: a) that the probes did not hybridrize in non-specific manner with the samples to analyse, b) that all the probes had similar hybridization characteristics, and c) that the signal of intensity obtained from each one of them can be related to the quantity of transcript added to the RNA. 
         [0171]    d) Hybridization Controls 
         [0172]    Snthetic oligonucleotides of DNA with 70 nucleotides (70-mer) were used As hybridization controls, modified at one end with a biotin molecule. These molecules are added in the same quantity to the sample just before hybridization, so that their value only depends on the processes of hybridization, developing and capture of images of the microarray. For each one of these 70-mer oligonucleotides, on the microarray there are several copies of an oligonucleotide with 50 nucleotides in length (50-mer), complementary to the corresponding 70-mer oligonucleotide with which it must hybridize. The 50-mer oligonucleotides which form part of the microarray and which are complementary to 70-mer oligonucleotides which are added to the cRNA before hybridizing are of codes SCN2, SCN3, SCN6, SCN8, SCN11, SCN12 and 
         [0173]    SCN13. To ensure low homology with human sequences, the sequences of these oligonucleotides were obtained from sequences of  Arabidopsis thaliana  and  Tripanosoma brucei . Their characteristics appear in Table 5 
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 5 
               
             
             
               
                   
               
               
                 Oligonucleotides used in the microarray as positive hybridization controls 
               
             
          
           
               
                 50-mer 
                   
                   
                   
                   
               
               
                 oligonucleotide 
                   
                   
                   
                 Complementary 
               
               
                 present in 
                   
                   
                 GenBank 
                 70-mer 
               
               
                 the microarray 
                 SEQ ID NO: 
                 Source gene 
                 code 
                 oligonucleotide 
               
               
                   
               
               
                 SCN2 
                 SEQ ID NO: 572 
                 Alpha-1.4- 
                 AY026941 
                 C2 
               
               
                   
                   
                 fucosyltransferase (FT4-M) 
                   
                   
               
               
                   
                   
                 from  Arabidopsis thaliana   
                   
                   
               
               
                 SCN3 
                 SEQ ID NO: 573 
                 mRNA of the 
                 AJ239128 
                 C3 
               
               
                   
                   
                 thioredoxine of 
                   
                   
               
               
                   
                   
                 
                   Tripanosoma brucei 
                 
                   
                   
               
               
                 SCN6 
                 SEQ ID NO: 576 
                 mRNA from a supposed 
                 AY051079 
                 C6 
               
               
                   
                   
                 expression protein of the 
                   
                   
               
               
                   
                   
                 RBP (complete CDS) 
                   
                   
               
               
                   
                   
                 from  Arabidopsis thaliana   
                   
                   
               
               
                 SCN8 
                 SEQ ID NO: 578 
                 mRNA from a supposed 
                 AY045879 
                 C8 
               
               
                   
                   
                 transfer protein of lipids 
                   
                   
               
               
                   
                   
                 (At1g48750) (complete 
                   
                   
               
               
                   
                   
                 CDS) from  Arabidopsis thaliana   
                   
                   
               
               
                 SCN11 
                 SEQ ID NO: 581 
                 mRNA from a supposed 
                 AY045879 
                  C11 
               
               
                   
                   
                 transfer protein of lipids 
                   
                   
               
               
                   
                   
                 (At1g48750) (complete 
                   
                   
               
               
                   
                   
                 CDS) from  Arabidopsis thaliana   
                   
                   
               
               
                 SCN12 
                 SEQ ID NO: 582 
                 mRNA from a supposed 
                 AY045879 
                  C12 
               
               
                   
                   
                 transfer protein of lipids 
                   
                   
               
               
                   
                   
                 (At1g48750) (complete 
                   
                   
               
               
                   
                   
                 CDS) from  Arabidopsis thaliana   
                   
                   
               
               
                 SCN13 
                 SEQ ID NO: 583 
                 mRNA of the papain- 
                 AF191028 
                  C13 
               
               
                   
                   
                 type cysteine endopeptidase 
                   
                   
               
               
                   
                   
                 XCP2 (complete CDS) 
                   
                   
               
               
                   
                   
                 from  Arabidopsis thaliana   
               
               
                   
               
             
          
         
       
     
         [0174]    For the design of the 50-mer oligonucleotides it was verified, in a manner similar to that previously described for the “Spiked controls”, that the oligonucleotides to be used did not hybridize in non-specific form with the samples to be analysed, that all the probes had similar hybridization characteristics and that the signal of intensity obtained from each one of them could be related to the quantity of the corresponding 70-mer oligonucleotide added to the cRNA. This made it possible to take as valid the oligonucleotides indicated in Table 5. The SCN4 (SEQ ID NO:574) and SCN9 (SEQ ID NO:579) oligonucleotides, designed in principle to act as hybridization controls, were seen to produce specific hybridization when human cRNA hybridized, for which reason they also appear in the microarray, as if they were probes which represent a human gene, but they are not taken into account as positive hybridization controls. For their part, oligonucleotides SCN1 (SEQ ID NO:571), SCN5 (SEQ ID NO:575), SCN7 (SEQ ID NO:577) and SCN10 (SEQ ID NO:580), which did not hybridize either in non-specific form with the samples, are also present in the microarray as negative hybridization controls, as no oligonucleotide complementary thereto were added to the cRNA. 
         [0175]    For its part, the hybridization controls solution, which contained the 70-mer oligonucleotides complementary to the 50-mer oligonucleotides present in the microarray as positive hybridization controls, was prepared from the corresponding biotinylated 70-mer sequences using a different concentration for each one of them, as shown in Table 6: 
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 6 
               
             
             
               
                   
               
               
                 Composition of the positive hybridization controls solution 
               
             
          
           
               
                 70-mer 
                   
                   
                   
               
               
                 Oligonucleotide 
                   
                 Complementary 
                 Concentration (pM) 
               
               
                 added to the 
                   
                 50-mer 
                 in the hybridization 
               
               
                 cRNA 
                 SEQ ID NO: 
                 oligonucleotide 
                 control solution 
               
               
                   
               
               
                 C2 
                 SEQ ID NO: 591 
                 SCN2  
                  750 
               
               
                 C3 
                 SEQ ID NO: 592 
                 SCN3  
                  250 
               
               
                 C6 
                 SEQ ID NO: 593 
                 SCN6  
                 1500 
               
               
                 C8 
                 SEQ ID NO: 594 
                 SCN8  
                 1250 
               
               
                 C11 
                 SEQ ID NO: 595 
                 SCN11 
                 2000 
               
               
                 C12 
                 SEQ ID NO. 596 
                 SCN12 
                 4500 
               
               
                 C13 
                 SEQ ID NO: 597 
                 SCN13 
                 2500 
               
               
                   
               
             
          
         
       
     
       Blanks 
       [0176]    Dimethyl sulfoxide (DMSO) without any probe was used, as this is the solvent wherein the oligonucleotides are found at the time of being deposited on the surface of the microarray. 
       Description of the Microarray Device 
       [0177]    Twelve replicas of each probe were deposited in different localizations on the surface of a solid support (glass in similar form to a microscope slide) using Microgrid II Spoter (Biorobotics). The 12 replicas of each probe were distributed on the support at random: 6 in the upper area and 6 in the lower area. Aminosylanized glass (Corning) was used as solid support. The moisture and the temperature were controlled throughout the printing process. 
         [0178]    The covalent binding of the probes to the solid supports was carried out by cross-linking by ultraviolet radiation using the “Stratalinker” apparatus (Stratagene). 
         [0179]    The quality control of the production process of the microarrays was the following: a) In each production run a microarray was stained with ethydium bromide which made it possible to analyze the size and form of the points printed. b) Another array of each run was hybridized with an already hybridized cRNA, analysing the hybridization signal, the background noise and the reproducibility of the replicas. 
         [0180]    The characteristics of the array are shown below in Table 7: 
         [0000]    
       
         
               
             
               
               
             
           
               
                 TABLE 7 
               
               
                   
               
               
                 Characteristics of the microarray 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 Number of genes represented 
                 538 
               
               
                 Length of the oligonucleotides 
                 25-55 mer 
               
               
                 Strand analysed 
                 Sense 
               
               
                 Number of oligonucleotides per gene 
                 1 (except 21 genes which 
               
               
                   
                 are represented by 2 or 3 
               
               
                   
                 different oligonucleotides) 
               
               
                 Number of replicas of each oligonucleotide 
                 12 
               
               
                 Blank 
                 DMSO 
               
               
                 Integrity controls 
                 4 
               
               
                 Spiked controls (internal positive controls) 
                 7 
               
               
                 Positive hybridization controls 
                 9 
               
               
                 Negative controls 
                 11 
               
               
                 Total number of points 
                 8192 (32 areas × 16 × 16) 
               
               
                 Size of the microarray 
                 25 × 75 mm 
               
               
                 Area spotted 
                 16.38 × 17.82 mm 
               
               
                 Distance between points 
                 x- y- axis 360 μm 
               
               
                   
               
             
          
         
       
     
       Treatment of the Samples 
     Cell Cultures 
       [0181]    Cultures of Jurkat cells (cell line from Leukemia T) and U937 (cell line from promonocytic leukemia) were centrifuged for 10 minutes at 1200 rpm and, after decanting the supernatant, the precipitate was resuspended in RNAlater (Ambion Inc) and it was stored at −80° C. at the time of extraction of the RNA. The RNA was extracted with TRIzol (Gibco-BRL Carlbad, Calif., USA) following the manufacturer&#39;s recommendations. 
       Blood Samples 
       [0182]    The blood samples were directly collected in PAXgene Blood RNA Tubes-PreAnalytix (Qiagen) tubes. 2.5 ml of blood were extracted in each tube and two tubes per individual. The tubes were inverted several times to allow the blood to mix with the stabilizing liquid which the tube contains, and they were stored at −20° C. until the night before RNA extraction. 
       Extraction of the Total RNA 
       [0183]    The tubes with the sample were incubated at ambient temperature during the night previous to the RNA extraction. The PAXgene Blood RNA kit (Qiagen) was used for the extraction following the manufacturer&#39;s recommendations, including the intermediate step of treatment with DNase (RNase-Free DNase Set, Quiagen) in column. The RNA of each extraction tube was eluted in 80 μl of BR5 buffer. The RNA of the two tubes which correspond to each patient was gathered in a single tube. 
       Purification of the Total RNA 
       [0184]    To ensure that the RNA obtained is free from free from contaminants that can interfere in later labelling reactions, it was purified in the following way: 16 μl (0.1 vol) of 7.5 M sodium acetate (Sigma) and 400 μl (2.5 vol) of 100% ethanol were added to 160 μl of total RNA solution. The solution was mixed in a “vortex” stirrer and it was incubated for 1 hour at −20° C. After 20 minutes of centrifugation at 12,000×g at 4° C., the precipitate was washed twice with 500 μl of 80% ethanol and it was resuspended in 35 μl of Rnase-free water. The RNAs obtained were stored at −80° C. until their later use. 
       Quantification of the Total RNA 
       [0185]    The quantification of the total RNA was carried out by the measurement of the absorbance at 260 nm in a spectrophotometer (DU 65, Beckman Coulter). 2 μl of the total RNA solution were diluted in 98 μl of 1 mM Tris-HCl pH 7.5 and the concentration was estimated (μg/ml) taking into account that 1 Unit of Optical Density at 260 nm corresponds to a RNA concentration of 44 μg/ml. 
       Determination of the Purity and Quality of the RNA 
       [0186]    The degree of purity was established from the absorbance ratio A260/A280 (nucleic acid/proteins), considering that the RNA is suitable, of “good quality”, when the A260/A280 ratio is between 1.9 and 2.1. 
         [0187]    The quality of the total RNA was determined by viewing the RNA after electrophoresis. 500 ng of total RNA were subjected to electrophoresis in 1% agarose gel (FMC) in TAE 1× buffer with BrEt (0.5 mg/ml), under a potential differenceof 100V for 25 minutes in AC electrophoresis cuvettes (BioRad). As marker of molecular weights, phage φ29 digested with the BamH I restriction enzyme was used. The gels were viewed in a Gel Doc (BioRad) ultraviolet light transiluminator. 
       Sample Labelling 
       [0188]    The choice of the strand with sense as probe limited the labelling strategy at those approximations which yield an antisense labelled product (complementary to the probe immobilized on the solid support). 
         [0000]    cRNA Labelling 
         [0189]    This type of labelling was performed during the course of an amplification process which consists of the use for the synthesis of single-strand cDNA, of an oligo(dT) primer which contains a promoter for the polymerase RNA enzyme of the T7 phage, an enzyme which will be used in the sample amplifications step. 
         [0190]    a.—cDNA synthesis: step wherein DNA (cDNA) complementary to the starting mRNA was synthesized. 5 μg of total RNA was incubated with 2 μl of the “Spiked controls” solution and 100 pmol of T7-(dT)24 (Genset Corp) primer in final volume of 12 μl during 10 minutes at 70° C. in a thermoblock, the mixture was cooled on ice and 4 μl of 5× First Strand Buffer (Gibco BRL Life Technologies), 0.1M 2 μl DTT (Gibco BRL Life Technologies), 1 μl dNTP mix 10 mM (Gibco BRL Life Technologies) and 1 μl of SuperScript II RNase H RT (200 OR/μl) (Gibco BRL Life Technologies) were added. After 1 hour of incubation in a bath equipped with a thermostat (Selecta) at 42° C., the reaction was cooled on ice. 
         [0191]    b.—Double chain DNA synthesis (dsDNA): a double chain of DNA was synthesized from the cDNA synthesized in the previous step. To 20 μl of previous reaction were added 91 μl of Rnase-free water, 30 μl of “Second Strand Reaction buffer” (Gibco BRL Life Technologies), 3 μl 10 mM dNTPs (Gibco BRL Life Technologies), 10 U  E. coli  DNA Ligase (Gibco BRL Life Technologies), 40 O  E. coli  DNA polymerase I (Gibco BRL Life Technologies), 2 U  E. coli  RNase H (Gibco BRL Life Technologies) in a final volume of 150 μl. The reaction was incubated in a thermoblock at 16° C. for 2 hours. Next, 10 U of T4 DNA Polymerase (Gibco BRL Life Technologies) were added and the mixture was incubated at 16° C. for 5 minutes. To stop the reaction, 10 μl of 0.5 M EDTA were added. 
         [0192]    c.—Purification of the dsDNA: To eliminate possible remains of reaction products which may interfere in later labelling reactions, the DNA obtained through phenol/chloroform extraction and later precipitation was purified. To 162 μl of previous reaction 162 μl of phenol: chloroform: isoamilic alcohol solution (25:24:1) (Ambion) were added. It was centrifuged for 2 min at 12,000×g in a centrifuge at ambient temperature, the upper aqueous phase was collected. To this upper phase 0.5 volumes of 7.5M ammonium acetate (Sigma Chemical) and 2.5 volumes of 100% ethanol cooled to −20° C.) were added. After stirring with “vortex” to mix well the components and centrifugation for 20 minutes at 12000×g at ambient temperature, the supernatant was eliminated and the precipitate was washed twice with 80% ethanol. The DNA obtained was resuspended in 10 μl of RNase-free water and it was concentrated in a “Speed-Vac” concentrator to a volume of 2 μl. This DNase was stored at −20° C. until its later use. 
         [0193]    d.—Synthesis and labelling of the cRNA: This reaction was carried out in a volume of 20 μl and using the T7 Megascript kit (Ambion), following the manufacturer&#39;s instructions and incorporating nucleotides modified with biotin, Bio-11-CTP and Bio-11 UTP (Perkin Elmer) in non-modified nucleotide/modified nucleotide ratio of 1:3. The reaction was incubated during 5 h and 15 minutes in a bath with thermostat (Selecta) at 37° C., stirring the reaction every 45 minutes. After this incubation, 1 μl of DNase was added and it was incubated for 30 min at 37° C. 
         [0194]    e.—Purification of the biotinylated cRNA: The biotinylated cRNA was purified with the RNeasy Total RNA Isolation Kit (Qiagen) following the manufacturer&#39;s instructions. The biotinylated cRNAs obtained were eluted in a volume of 80 μl and they were stored at −80° C. until its later use. 
         [0195]    The quantity, purity and quality of the cRNA obtained were determined following the same methods described for the total RNA. 
         [0196]    The cRNA was stored at −80° C. until its later use. 
         [0000]    Fragmentation of the Biotinylated cRNA 
         [0197]    10 μg of biotinylated cRNA were fragmented in the presence of 5× (200 mM Tris-acetate, pH 8.1, 500 mM HOAC, 150 mM MgOAc) fragmentation buffer during 35 minutes at 94° C. in a thermoblock. It was verified that the fragmentation reaction had been carried out by viewing 1 μl of fragmentation solution in electrophoresis on 1% agarose gel. 
         [0000]    Hybridization of the cRNA Labelled with the Probes of the Microarray 
         [0198]    In this step the labelled genetic material were placed in contact with the probes immobilized on the solid support. 
         [0199]    10 μl of the hybridization control solution were added to the biotinylated and fragmented cRNA solution and the mixture was incubated for 3 min at 95° C. to denature the possible secondary structures. After incubation, the mixture was immediately taken to ice to prevent the possible renaturing of the sample. 
         [0200]    The hybridization was carried out for 6 hours at 42° C. in the Ventana Discovery automatic hybridization station (Ventana Medical Systems). The hybridization and washing buffers were supplied by Ventana Medical System. The microarrays were automatically stained in the hybridization station with streptavidin conjugated with Cy3 (Amersham Biosciences) using the manufacturer&#39;s recommendations. 
       Capture of Images and Quantification of the Microarrays 
       [0201]    After the hybridization and developing, the images of the microarrays were identified and analysed by the ScanArray 4000 confocal fluorescent scanner (Perkin Elmer) equipped with a laser for the green (543 nm to excite the fluorophore Cy3). The “software” used was ScanArray 3.1. The use of the computer programme QuantArray 3.0 (Perkin Elmer) provided the absolute values of the intensity of hybridization and background noise in accordance with the light emitted by the Cy3 in each probe in an Excel format. 
       Data Analysis: Preliminary Processing 
       [0202]    In first place, the value of the background noise were subtracted from the values of absolute intensity of all the oligonucleotides. To do this, the values of absolute intensity and the values of background noise, which the programme used to convert the signals of the fluorophore returns, automatically, were used for each one of the microarray points: the corresponding in tensity value is obtained from the zone which has been defined as point and the value of the background noise is obtained from the zone situated around the point. 
         [0203]    Next, the average level of hybridization intensity of each one of the oligonucleotides of the microarray was calculated from the trimmed mean of the intensities of the 12 replicas of each one of the oligonucleotides. To do this, before calculating the average, the upper and lower values of the distribution points of hybridization signals obtained with each one of the replicas of the same oligonucleotide have to be eliminated. The calculation was performed using the Excel programme from Microsoft and, specifically, the TRIMMEAN function thereof, wherein the “percentage” parameter was set at 0.2, which supposes fixing the percentage of values eliminated in 20% of the upper values and 20% of the lower values; the function rounds up the number of data points excluded to the closest multiple of 2. 
         [0204]    In last place, and to be able to determined the validity of the hybridization, it is necessary that a series of established criteria are met: 1) the ratio between the average intensity and the aver age background of all the oligonucleotides of the chip is greater than 10; 2) the value of the average coefficient of variation (standard deviation of the replicas compared with the average of the replicas) of all the replicas of oligonucleotides of the chip should be less than 0.3; 3) the average value of the negative control should be less than 2.5 times the value of the DMSO medium; 4) a signal should be obtained both in the hybridization controls and in the exogenous internal positive controls (Spiked controls). 
         [0205]    The data analysis was performed in R, version 1.9.1. R is a programming language wherein both classical and modern statistical techniques can be applied (R Developmental Core Team, 2004; http://www.R-project.org), which has a series of functions stored in packages for the handling, calculation and graphic representation of data (Venables et al., 2004). There are hundreds of packages written by different authors for R, with special statistical functions or which permit the access and handling of data and are available for downloading from the websites of CRAN (http://cran.r-project.org/) or Bioconductor (http://www.bioconductor.org). In some specific cases, the SPSS commercial statistical analysis software was used (Chicago, USA). 
       EXAMPLES 
     Example 1 
     Results Obtained on Using the Microarray Device with Samples of U937 Vs Jurkat Cells 
       [0206]    In order to know if the device permits differentiating two cells lines hybridized in 10 microchips: 5 samples of biotinylated cRNAs synthesized following the optimized working protocol, obtained from RNA of U937 cells (cell line from promonocytic leukemia) and 5 samples of biotinylated cRNAs obtained from RNA of Jurkat cells (cell line from T Leukemia). 
         [0207]    The initial steps of preliminary processing of the data and validation of the hybridization mentioned previously in the “Data analysis: Preliminary processing” section were carried out and then the data was normalized and filtered:
       Data normalization. The “variance stabilization normalization” method was used, available in the “vsn” package in R. There are different packages available on the Internet for R, with special statistical functions or which permit the access and processing of data and are available for downloading from CRAN (http://cran.r-project.orq/) or Bioconductor (http://www.bioconductor.orq)   ata filtering. Two filtering operations have been carried out with the “Filterfun” function of the of the “Genefilter” filter in R. The genes which did not pass any of the two filters were not used in the data analysis. The filters carried out were:
           Filtering to exclude genes with an intensity value close to the DMSO. This filter made it possible to work with genes with an intensity value minus average background noise greater than 550 arbitrary units (approximately 2 times the value of the DMSO).   Filtering to exclude genes with minimum intensity variation throughout the samples. Genes were worked with an interquartile range of normalized intensity throughout samples greater than 0.3.   
               
 
         [0212]    The data filtering left 83 probes which constituted the working list. With them a grouping was made of the non-supervised samples, which are those groupings wherein the structure of the data is not previously known, the system learning how the data are distributed among classes based on a distance function. A tree or hierarchical group was obtained with the grouping, wherein the samples are grouped in accordance with their similarity in the expression of certain genes, those corresponding to the oligonucleotides of the working list, so that the closest samples are those which have a similar expression profile. The grouping was performed with the hclust function of the stats package in R. The non-supervised analysis of the 10 samples produced their separation in two groups or main branches in accordance with the cell type whereto the samples belong: a group contains the 5 hybridizations carried out from U937 cells and the other group contains the 5 hybridizations carried out from Jurkat cells. The resulting tree of this non-supervised grouping is shown in part A of  FIG. 1 . 
         [0213]    Next, to find out if there were statistically significant differences between the two groups of samples, the “Step-down maxT multiple testing methods” method (maxT) was used, which is an application of the mt.maxT function of the multtest package of the software in R from Bioconductor, which applies a statistical test and carries out a strong control over the rate of false positives. To this function, the following should be provided: 
         [0214]    a) Values on which one wants to apply the statistical tests, in this case, on the normalized values of the 83 oligonucleotides which passed the filters 
         [0215]    b) Groups of which one wants to seek differences, in this case the 5 samples of Jurkat cells against the 5 samples of cells U937 
         [0216]    c) Number of permutations one wants to perform. In this case, 100,000 permutations are carried out. 
         [0217]    d) By default, Welch&#39;s test was chosen to specify the statistical tool to be used to test the hypothesis of non-association between the variables and the class labels. 
         [0218]    The application of this analysis with a value of p&lt;0.001 provided a list of 69 statistically significant probes between the two groups, which are the following:
       SG12, SG20, SG23, SG24, SG38, SG39, SG45, SG49, SG53, SG59, SG60, SG62, SG76, SG78, SG89, SG92, SG94, SG102, SG474, SG478, SG487, SG114, SG120, SG140, SG142, SG145, SG150, SG154, SG158, SG174, SG175, SG194, SG195, SG211, SG230, SG231, SG235, SG260, SG264,   SG266, SG268, SG270, SG272, SG282, SG294, SG308, SG311, SG330, SG332,   SG333, SG339, SG344, SG364, SG403, SG423, SG434, SG456, SG506, SG513, SG514, SG515, SG524, SG533, SG538, SG541, SG559       
 
         [0222]    Once the statistically significant genes to distinguish between the two groups of samples are known (which would be the genes corresponding to the probes identified as statistically significant) the supervised grouping was carried out of the samples in accordance with the intensity of the signal of the 69 statistically significant probes obtained. The term “supervised”, applied to a grouping, makes reference to the fact that the data structure is previously known, which makes it possible to use the prior information; with this, after a training process which allows the system to learn to distinguish between classes, it is possible to use the network to assign new members to the predefined classes. In this case, the supervised grouping of the samples in accordance with the intensity of the signal obtained with the 69 statistically significant probes obtained, is again a tree which is divided in two main branches in accordance with the cell type to which the samples belong. The tree obtained with the supervised grouping is shown in part B of  FIG. 1 . 
       Example 2 
     Results Obtained on Using the “Array” Device with Samples from Healthy Subjects Vs U937 and Jurkat Cells 
       [0223]    The expression of 5 samples of U937 cells and 5 samples of Jurkat cells was compared with the expression of 10 samples from total blood from healthy subjects. In a manner similar to that carried out in Example 1, the initial data processing steps, validation of the hybridizations, normalization and filtering were carried out. A total of 180 genes passed the filtering processes. The non-supervised grouping of the samples (carried out with the hclust function of the stats package of R applying Pearson&#39;s correlation) in accordance with the expression of the 180 genes, provided a tree with two main branches: one branch contains all the samples from cell cultures and the other branch contains all the samples from total blood from healthy subjects, which demonstrates that the tool is capable of finding expression differences. The tree obtained after making this non-supervised grouping is shown in part A of  FIG. 2 . 
         [0224]    The maxT test (p&lt;0.001) to find genes with statistically significant differences between the samples from U937 and Jurkart cell cultures and the 10 samples from total blood of healthy subjects was performed. The statistical analysis provided a list of 131 probes with statistically significant differences between both groups of samples. They are the following: 
         [0000]    SG1, SG4, SG7, SG8, SG10, SG13, SG15, SG16, SG17, SG18, SG19, SG20, SG26, SG29, SG30, SG34, SG36, SG39, SG42, SG44, SG49, SG51, SG52, SG58, SG64, SG65, SG67, SG76, SG77, SG80, SG84, SG86, SG89, SG92, SG93, SG94, SG98, SG99, SG101, SG102, SG107, SG463, SG464, SG474, SG475, SG485, SG487, SG466, SG467, SG471, SG472, SG473, SG120, SG129, SG138, SG141, SG144, SG145, SG147, SG158, SG163, SG164, SG176, SG185, SG186, SG197, SG207, SG208, SG217, SG227, SG231, SG265, SG266, SG277, SG278, SG283, SG285, SG299, SG307, SG308, SG311, SG313, SG318, SG319, SG328, SG333, SG336, SG342, SG344, SG357, SG361, SG376, SG384, SG389, SG395, SG398, SG403, SG404, SG407, SG416, SG420, SG423, SG430, SG436, SG446, SG455, SG461, SG489, SG491, SG492, SG493, SG498, SG500, SG504, SG505, SG506, SG514, SG516, SG517, SG520, SG526, SG530, SG533, SG538, SG545, SG547, SG554, SG555, SG558. 
         [0225]    The grouping of the 20 samples, in accordance with the expression of the statistically significant probes found, gave rise again to a tree with two main branches, one corresponding to the samples from cell cultures and another corresponding to the samples from healthy individuals. Said grouping appears in part B of  FIG. 2 . 
       Example 3 
     Results Obtained with Samples from Patients with Chronic Lymphatic Leukemia (CLL) Vs U937 and Jurkat Cells 
       [0226]    The expression profiles were compared of samples from U937 and Jurkats cell cultures with 26 samples from total blood of subjects with CLL. 
         [0227]    The samples underwent preliminary processing of the data, they were normalized and filtered in a manner analogous to those used in Examples 1 and 2 and a total of 236 probes passed through the filters. The non-supervised grouping of the samples in accordance with the expression of the probes which passed through the filters showed a tree with two main branches: one which contained the samples of cell cultures and the other the CLL samples. Said tree is shown in part A of  FIG. 3 . 
         [0228]    The maxT test (p&lt;0.001) to find genes with statistically significant differences between the two groups of samples was carried out. This analysis provided a list of 120 probes. They are the following: SG2, SG4, SG8, SG10, SG13, SG15, SG16, SG19, SG20, SG23, SG26, SG28, SG31, SG34, SG36, SG39, SG48, SG58, SG60, SG65, SG76, SG77, SG84, SG89, SG94, SG9, SG97, SG99, SG102, SG106, SG107, SG463, SG464, SG474, SG475, SG481, SG465, SG485, SG487, SG466, SG467, SG471, SG473, SG115, SG116, SG117, SG120, SG129, SG134, SG135, SG138, SG139, SG141, SG145, SG158, SG161, SG163, SG176, SG178, SG185, SG207, SG208, SG210, SG217, SG227, SG231, SG237, SG264, SG272, SG277, SG281, SG283, SG286, SG294, SG298, SG299, SG307, SG308, SG319, SG328, SG330, SG333, SG336, SG342, SG344, SG345, SG347, SG361, SG384, SG389, SG395, SG404, SG407, SG416, SG423, SG428, SG430, SG432, SG434, SG444, SG446, SG453, SG458, SG459, SG491, SG498, SG507, SG508, SG511, SG517, SG518, SG522, SG526, SG530, SG533, SG538, SG541, SG554, SG558, SG561. 
         [0229]    The grouping of the 30 samples in accordance with the expression of the 120 statistically significant probes found again gave rise to a tree with two main branches, one corresponding to the samples from cell cultures and another corresponding to the samples from healthy individuals. Said grouping appears in part B of  FIG. 3 . 
       Example 4 
     Results Obtained with Samples from Healthy Subjects Vs Patients with Chronic Lymphatic Leukemia (CLL) 
       [0230]    68 hybridizations which met the quality criteria from 68 samples of different healthy subjects and with clinical diagnosis of CLL were divided in 2 groups: Training Group used to obtain the functions of the classifier and Test Group, used to test the classifier obtained. The Training group was composed of 30 samples (10 from healthy subjects and 20 from CLL subjects) and the Test Group was composed of 38 samples (5 samples from healthy subjects and 33 samples from subjects with CLL). 
         [0231]    To obtain the classification function, the results obtained from the hybridizations of the Training group were worked with. The steps carried out to obtain the classification function were:
       Data normalization. The “variance stabilization normalization” method, available in the “vsn” package in R, was used.   Data filtering. Two filtering operations have been carried out with the “Filterfun” function of thee “Genefilter” package in R. The genes which did not pass any of the two filters were not used in the data analysis. From the 588 oligonucleotides of the chip, 224 passed through the 2 filters and constituted the working list.   2. Filtering to exclude genes with an intensity value close to the DMSO. This filter made it possible to work with genes with an intensity value minus average background noise greater than 550 arbitrary units (approximately 2 times the value of the DMSO) in more than 25% of the samples (7 samples) which compose the Training group.   3. Filtering to exclude genes with minimum intensity variation throughout the samples. Genes were worked with which had an interquartile range of normalized intensity throughout samples greater than 0.3.       
 
         [0236]    Two classification systems are used: 
         [0237]    4.1.—Construction of a Classification System with PAM. 
         [0238]    To identify groups of genes which best characterize each type of sample and verify the classification rate of these groups of genes Prediction Analysis for Microarrays (PAM) was used, available as “pamr a ” package in R. It is a statistical technique which identifies a group of genes which best characterizes a predefined class and uses this group of genes to predict the class whereto new samples belong. PAM uses a modified version of the “nearest centroids” classification method (Tibshirani et al., 2002) called “Nearest Shrunken Centroids”. A validation called “10 fold cross validation” was performed, which consists of constructing the model with 90% of the samples and an attempt is made to predict the class of 10% of the samples which have not intervened in the construction of the model. This method is repeated 10 times and the classification error of 10% of the samples is added to calculate the overall error. This error reflects the number of badly classified samples (Bullinger et al., 2005). 
         [0239]    4.1.1. Construction of the model. From the filtered and normalized data of the 30 samples which compose the Training group, attributing in an arbitrary form the Healthy Group to group 0 and the CLL Group to group 1, performing the 10 cross-validations and with a threshold value of Delta 3.1. The model obtained was formed by the following oligonucleotides: SG459, SG428, SG507, SG508, SG117, SG237. The coefficients of the classifier corresponding to each one of these oligonucleotides are shown below in Table 8: 
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 8 
               
             
             
               
                   
               
               
                 Coefficients of the PAM classifier 
               
             
          
           
               
                 id 
                 Value 0 
                 Value 1 
               
               
                   
               
               
                 [1,] SG459 
                 −0.4344 
                 0.2172 
               
               
                 [2,] SG428 
                 −0.146  
                 0.073  
               
               
                 [3,] SG507 
                 −0.1111 
                 0.0555 
               
               
                 [4,] SG508 
                 −0.1044 
                 0.0522 
               
               
                 [5,] SG117 
                 −0.1003 
                 0.0502 
               
               
                 [6,] SG237 
                 −0.0539 
                 0.027  
               
               
                   
               
             
          
         
       
     
         [0240]    4.1.2. Validation of the PAM classifier. The cross-validation of the samples which compose the Training group correctly classified 28 of the 30 samples. 
         [0241]    From the filtered and normalized data of the 38 samples which compose the Test Group, probability values p were obtained belonging to group 0 (healthy group) or group 1 (CLL group). The greater the value of p, the greater the probability of belonging to that group. It has been considered that the values greater than 0.5 indicate belonging to that group. The values of p obtained for each sample are indicated in Table 9. 
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 9 
               
             
             
               
                   
               
               
                 Probability values obtained with the PAM classifier for the Test Group 
               
             
          
           
               
                 Sample 
                 p (Group 0) 
                 p (Group 1) 
                   
               
               
                   
               
               
                 S229 
                 0.8031905 
                 0.1968095 
                   
               
               
                 S231 
                 0.7403173 
                 0.2596827 
                   
               
               
                 S232 
                 0.8810574 
                 0.1189426 
                   
               
               
                 S233 
                 0.7973159 
                 0.2026841 
                   
               
               
                 S251 
                 0.8714224 
                 0.1285776 
                   
               
               
                 CLL166 
                 0.3764637 
                 0.6235363 
                   
               
               
                 CLL184 
                 0.1278230 
                 0.8721770 
                   
               
               
                 CLL132 
                 0.2081423 
                 0.7918577 
                   
               
               
                 CLL210 
                 0.3248082 
                 0.6751918 
                   
               
               
                 CLL213 
                 0.3536033 
                 0.6463967 
                   
               
               
                 CLL214 
                 0.2705277 
                 0.7294723 
                   
               
               
                 CLL221 
                 0.3650277 
                 0.6349723 
                   
               
               
                 CLL208 
                 0.2323872 
                 0.7676128 
                   
               
               
                 CLL225 
                 0.4034316 
                 0.5965684 
                   
               
               
                 CLL236 
                 0.4893545 
                 0.5106455 
                   
               
               
                 CLL240 
                 0.3807527 
                 0.6192473 
                   
               
               
                 CLL168 
                 0.1616066 
                 0.8383934 
                   
               
               
                 CLL172 
                 0.2002317 
                 0.7997683 
                   
               
               
                 CLL174 
                 0.1601147 
                 0.8398853 
                   
               
               
                 CLL175 
                 0.6009558 
                 0.3990442: 
                 →Only badly classified sample 
               
               
                 CLL177 
                 0.1634185 
                 0.8365815 
                   
               
               
                 CLL179 
                 0.2300440 
                 0.7699560 
                   
               
               
                 CLL181 
                 0.2177406 
                 0.7822594 
                   
               
               
                 CLL182 
                 0.3450880 
                 0.6549120 
                   
               
               
                 CLL164 
                 0.2590083 
                 0.7409917 
                   
               
               
                 CLL159 
                 0.3688586 
                 0.6311414 
                   
               
               
                 CLL142R 
                 0.2111712 
                 0.7888288 
                   
               
               
                 CLL105 
                 0.2962797 
                 0.7037203 
                   
               
               
                 CLL107 
                 0.3764637 
                 0.6235363 
                   
               
               
                 CLL109 
                 0.3525788 
                 0.6474212 
                   
               
               
                 CLL112 
                 0.2059187 
                 0.7940813 
                   
               
               
                 CLL151 
                 0.2951067 
                 0.7048933 
                   
               
               
                 CLL158 
                 0.1932882 
                 0.8067118 
                   
               
               
                 CLL169 
                 0.3525937 
                 0.6474063 
                   
               
               
                 CLL171 
                 0.1495153 
                 0.8504847 
                   
               
               
                 CLL178 
                 0.2260191 
                 0.7739809 
                   
               
               
                 CLL111 
                 0.2951168 
                 0.7048832 
                   
               
               
                 CLL155 
                 0.2832151 
                 0.7167849 
               
               
                   
               
             
          
         
       
     
         [0242]    With this model 37 of the 38 samples of the Test Group are correctly classified: all the samples corresponding to healthy individuals (those whose name is headed by the letter “S”) have a probability greater than 0.5 of belonging to group 0, whilst all the samples corresponding to individuals suffering from CLL (which are the samples whose name starts with letters “CLL”) minus one have a probability greater than 0.5 of belonging to group 1. 
         [0243]    4.2.—Construction of a Classification System with Logistical Regression. 
         [0244]    4.2.1.—Selection of genes with statistically significant differences among healthy and CLL (Training group). From the filtered and normalized data as has been previously described, the “Step-down maxT multiple testing methods” method (maxT) was used for the selection of genes with significant differences, which is an application of the mt.maxT function of the multtest package of the software in R from Bioconductor, which applies a statistical test and carries out a strong control over the rate of false positives. The application of this statistical test, with a value of p&lt;0.001, to the 224 oligonucleotides which passed through the filters, produced a list of 7 oligonucleotides: SG117, SG428, SG459, SG461, SG493, SG507, SG508. 
         [0245]    The steps used to obtain the list of 7 significant genes among healthy and CLL were:
       Method which makes permutations and adjusts the values of p resT&lt;-mt.maxT(exprs(224 oligonucleotides which have passed through the filters and normalized of the training group, Types of samples in the training group, test=“t”, B=100000): mt.maxT function which through permutations adjusts the probability values (signification) which entails a strong control of the rate of false positives.       
 
         [0247]    To this function the following should be provided: 
         [0000]    1. Values on which one wants to apply the statistical tests, in this case, on the normalized values of the 83 oligonucleotides which passed through the filters
 
2. Groups of which one wants to seek differences, in this case the 5 samples of Jurkat cells against the 5 samples of cells U937
 
3. Number of permutations one wants to perform. In this case, 100,000 permutations are carried out.
 
4. By default, Welch&#39;s test was chosen as statistical test.
 
         [0248]    The statistically significant genes at a level of p&lt;0.001 were selected by this test and a number of 7 was obtained. 
         [0249]    4.2.2.—Obtainment of the classification function with SPSS. By logistical regression from the normalized values of the 7 statistically significant oligonucleotides obtained from the 30 samples which compose the Training group and assigning in arbitrary manner group 0 to the healthy samples and group 1 to the CLL samples, the values of the classification function were obtained. The coefficients corresponding to each oligonucleotide were those which are shown below in Table 10: 
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 10 
               
             
             
               
                   
               
               
                 Coefficients of the classification function 
               
               
                 Calculated by logistical regression 
               
             
          
           
               
                   
                 Oligonucleotide 
                 Coefficients (Coeff) 
               
               
                   
                   
               
               
                   
                 SG117 
                   2.44756372 
               
               
                   
                 SG428 
                   7.38657611 
               
               
                   
                 SG459 
                  23.1465464 
               
               
                   
                 SG461 
                  43.6287742 
               
               
                   
                 SG493 
                  −19.3978182 
               
               
                   
                 SG507 
                  −2.80282646 
               
               
                   
                 SG508 
                  49.5345672 
               
               
                   
                 Constant 
                 −719.241486 
               
               
                   
                   
               
             
          
         
       
     
         [0250]    From these coefficients, for each sample i a value x i  is calculated as follows: 
         [0000]        x   i =Constant+(Coeff  ohle 0009* Imn   i   SG 117)+(Coeff  SG 428 *Imn   i   SG 428)+(Coeff  SG 459* Imn   i    SG 459)+(Coeff  SG 461* Imn   i   SG 461)+(Coeff  SG 493* Imn   i    SG 493)+(Coeff  SG 507 *Imn   i   SG 507)+(Coeff  SG 508 *Imn   i   SG 508). 
         [0251]    where Imn i  is the average value of normalized intensity of the sample i. 
         [0252]    From the value x i  a value of probability (p i ) is calculated. The closer the value of p is to 0, the greater the probability of belonging to the group of healthy subjects (assigned as group 0) and the closer the value of p is to 1, the greater the probability there is of the sample belonging to the group of CLL subjects (assigned as group 1). The formula used to determine the value of p is: 
         [0000]        p   i =1/(1 +e   −xi ). 
         [0253]    As is shown in Table 11, the function obtained correctly classified the 30 samples belonging to the training group. The closer to 0, the greater the probability that it is healthy and the closer to 1 the greater probability of CLL. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 11 
               
               
                   
               
             
             
               
                 Classification table a   
               
             
          
           
               
                   
                   
                   
                   
                 Prognosis 
               
             
          
           
               
                   
                   
                   
                   
                 EVOL 
                 Correct 
               
             
          
           
               
                   
                   
                 Observed 
                   
                 0 
                 1 
                 percentage 
               
               
                   
                   
               
               
                   
                 Step 1 
                 EVOL 
                 0 
                 10 
                  0 
                 100.0 
               
               
                   
                   
                   
                 1 
                  0 
                 20 
                 100.0 
               
               
                   
                   
                 Overall percentage 
                   
                   
                   
                 100.0 
               
               
                   
                   
               
               
                   
                   a The cut-off value is ,500 
               
             
          
         
       
     
         [0254]    4.2.3. Validation of the system classifier.—From the filtered and normalized filters as detailed above, the Imn i  values were obtained of the 7 oligonucleotides which compose the classifier of each one of the 38 samples which compose the Test Group. 
         [0255]    Results of the validation of the system classifier. Below, tables are shown wherein the Imn i  value is obtained of each one of the 7 oligonucleotides included in the classifier and the values of x i  and p i  calculated according to the formulas previously described, obtained for each one of the 38 samples of the Test Group. The samples which begin with S correspond to healthy subjects and the samples which start with CLL are from CLL subjects. 37 out of 38 samples are correctly classified. Only sample CLL175, for which a value of pi=0 is obtained is incorrectly classified. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 12 
               
               
                   
               
               
                 Results obtained with the Test Group by the classification function obtained by logistical regression 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 lmn i   
                 S229 
                 S231 
                 S232 
                 S233 
                 S251 
                 CLL166 
                 CLL184 
                 CLL132 
                 CLL210 
                 CLL213 
                 CLL214 
               
               
                   
               
               
                 SG117 
                 4.89 
                 5.17 
                 5.14 
                 5.33 
                 5.37 
                 6.17 
                 7.45 
                 7.05 
                 7.06 
                 6.88 
                 6.86 
               
               
                 SG428 
                 4.82 
                 4.80 
                 4.52 
                 4.69 
                 4.52 
                 5.74 
                 6.97 
                 6.46 
                 6.66 
                 6.08 
                 6.49 
               
               
                 SG459 
                 6.50 
                 6.95 
                 6.10 
                 6.59 
                 5.96 
                 8.11 
                 9.04 
                 8.71 
                 8.13 
                 8.15 
                 8.40 
               
               
                 SG461 
                 6.47 
                 6.41 
                 6.44 
                 6.43 
                 6.05 
                 6.35 
                 7.22 
                 6.99 
                 6.75 
                 6.75 
                 7.04 
               
               
                 SG493 
                 7.20 
                 7.31 
                 7.02 
                 7.16 
                 6.83 
                 7.53 
                 7.69 
                 7.35 
                 7.43 
                 7.35 
                 7.57 
               
               
                 SG507 
                 8.32 
                 7.82 
                 7.26 
                 7.77 
                 7.47 
                 9.11 
                 9.82 
                 9.32 
                 9.19 
                 8.49 
                 9.18 
               
               
                 SG508 
                 6.67 
                 6.82 
                 6.34 
                 6.82 
                 6.81 
                 7.79 
                 8.71 
                 7.80 
                 7.55 
                 7.66 
                 7.68 
               
               
                 x i   
                 −71.35 
                 −56.83 
                 −93.68 
                 −61.26 
                 −86.57 
                 17.23 
                 129.51 
                 70.11 
                 33.93 
                 38.26 
                 55.19 
               
               
                 p i   
                 0.00 
                 0.00 
                 0.00 
                 0.00 
                 0.00 
                 1.00 
                 1.00 
                 1.00 
                 1.00 
                 1.00 
                 1.00 
               
               
                   
               
             
          
           
               
                 lmn i   
                 CLL221 
                 CLL208 
                 CLL225 
                 CLL236 
                 CLL240 
                 CLL168 
                 CLL172 
                 CLL174 
                 CLL175 
                 CLL177 
               
               
                   
               
               
                 SG117 
                 7.00 
                 7.42 
                 6.91 
                 6.40 
                 6.76 
                 7.34 
                 7.32 
                 7.40 
                 5.32 
                 7.72 
               
               
                 SG428 
                 6.40 
                 6.98 
                 6.00 
                 6.24 
                 6.09 
                 6.77 
                 6.16 
                 7.49 
                 4.85 
                 6.38 
               
               
                 SG459 
                 7.93 
                 8.54 
                 8.01 
                 7.55 
                 8.19 
                 8.94 
                 8.86 
                 8.69 
                 7.72 
                 8.78 
               
               
                 SG461 
                 6.77 
                 7.18 
                 6.89 
                 6.79 
                 6.54 
                 6.72 
                 7.02 
                 7.18 
                 5.98 
                 6.86 
               
               
                 SG493 
                 7.14 
                 7.92 
                 7.72 
                 7.47 
                 6.73 
                 7.97 
                 7.96 
                 8.45 
                 7.16 
                 8.05 
               
               
                 SG507 
                 9.00 
                 8.98 
                 8.41 
                 8.74 
                 8.80 
                 9.53 
                 9.67 
                 10.09 
                 8.76 
                 9.76 
               
               
                 SG508 
                 7.50 
                 7.43 
                 7.22 
                 7.36 
                 6.90 
                 8.08 
                 7.38 
                 7.81 
                 6.43 
                 7.94 
               
               
                 x i   
                 31.80 
                 50.30 
                 12.52 
                 8.94 
                 3.77 
                 67.59 
                 39.95 
                 63.19 
                 −75.92  
                 59.42 
               
               
                 p i   
                 1.00 
                 1.00 
                 1.00 
                 1.00 
                 0.98 
                 1.00 
                 1.00 
                 1.00 
                 
                   0.00 
                 
                 1.00 
               
               
                   
               
             
          
           
               
                 lmn i   
                 CLL179 
                 CLL181 
                 CLL182 
                 CLL164 
                 CLL159 
                 CLL142R 
                 CLL105 
                 CLL107 
                 CLL109 
                 CLL112 
               
               
                   
               
               
                 SG117 
                 6.89 
                 6.92 
                 6.14 
                 8.03 
                 6.98 
                 6.80 
                 6.52 
                 6.17 
                 6.79 
                 7.31 
               
               
                 SG428 
                 6.32 
                 6.22 
                 5.64 
                 5.40 
                 5.55 
                 5.94 
                 6.05 
                 5.74 
                 5.81 
                 6.52 
               
               
                 SG459 
                 8.52 
                 8.71 
                 8.35 
                 8.54 
                 8.00 
                 8.87 
                 8.32 
                 8.11 
                 8.20 
                 8.77 
               
               
                 SG461 
                 6.83 
                 6.95 
                 6.87 
                 6.96 
                 6.63 
                 7.07 
                 6.72 
                 6.35 
                 6.66 
                 6.80 
               
               
                 SG493 
                 7.99 
                 7.92 
                 7.71 
                 7.73 
                 7.49 
                 7.96 
                 7.79 
                 7.53 
                 7.70 
                 7.99 
               
               
                 SG507 
                 9.40 
                 9.53 
                 9.37 
                 8.86 
                 9.34 
                 9.49 
                 9.49 
                 9.11 
                 8.89 
                 9.41 
               
               
                 SG508 
                 8.17 
                 8.18 
                 7.37 
                 7.80 
                 7.81 
                 7.97 
                 7.75 
                 7.79 
                 7.46 
                 7.69 
               
               
                 x i   
                 62.78 
                 73.52 
                 19.76 
                 53.03 
                 28.34 
                 68.92 
                 33.36 
                 17.23 
                 16.00 
                 45.86 
               
               
                 p i   
                 1.00 
                 1.00 
                 1.00 
                 1.00 
                 1.00 
                 1.00 
                 1.00 
                 1.00 
                 1.00 
                 1.00 
               
               
                   
               
             
          
           
               
                   
                 lmn i   
                 CLL151 
                 CLL158 
                 CLL169 
                 CLL171 
                 CLL178 
                 CLL111 
                 CLL155 
               
               
                   
                   
               
               
                   
                 SG117 
                 6.51 
                 7.26 
                 6.79 
                 7.76 
                 6.62 
                 6.51 
                 6.90 
               
               
                   
                 SG428 
                 6.14 
                 6.17 
                 5.81 
                 5.96 
                 5.97 
                 6.14 
                 5.44 
               
               
                   
                 SG459 
                 8.40 
                 8.81 
                 8.20 
                 9.18 
                 8.77 
                 8.40 
                 8.44 
               
               
                   
                 SG461 
                 6.64 
                 7.01 
                 6.66 
                 7.10 
                 6.79 
                 6.64 
                 6.71 
               
               
                   
                 SG493 
                 8.00 
                 8.12 
                 7.70 
                 8.03 
                 8.05 
                 8.00 
                 7.91 
               
               
                   
                 SG507 
                 9.11 
                 9.36 
                 8.89 
                 9.52 
                 9.36 
                 9.11 
                 9.35 
               
               
                   
                 SG508 
                 7.87 
                 8.29 
                 7.46 
                 7.99 
                 8.06 
                 7.87 
                 8.23 
               
               
                   
                 x i   
                 35.32 
                 81.12 
                 16.00 
                 79.33 
                 57.33 
                 35.32 
                 53.92 
               
               
                   
                 p i   
                 1.00 
                 1.00 
                 1.00 
                 1.00 
                 1.00 
                 1.00 
                 1.00 
               
               
                   
                   
               
             
          
         
       
     
         [0256]    A third group of 40 samples was formed. To do this, replicas of hybridization or of labelling were used (the samples whose name begins with S and Strans are samples from people considered healthy and those which start with CLL are samples from patients with chronic lymphatic leukemia). This group of samples was used to validate the classification system. The data were normalized as has been previously described. The results of the classification are shown in the Table 13. 40 out of the 40 samples are correctly classified. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 13 
               
               
                   
               
               
                 Results obtained in the validation of the classification function obtained by logistical regression 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 lmn i   
                 S120.7 
                 S120.14 
                 Strans.3 
                 Strans.4 
                 S150.2 
                 S228.6 
                 S229.7 
                 CLL142.8 
                 CLL147.9 
                 S120.7 
               
               
                   
               
               
                 SG117 
                 5.22 
                 5.40 
                 5.41 
                 4.95 
                 5.47 
                 6.05 
                 5.34 
                 7.06 
                 5.39 
                 5.22 
               
               
                 SG428 
                 4.95 
                 4.64 
                 4.29 
                 4.20 
                 5.01 
                 3.89 
                 5.07 
                 6.31 
                 5.59 
                 4.95 
               
               
                 SG459 
                 6.39 
                 6.14 
                 5.46 
                 4.98 
                 7.14 
                 5.72 
                 6.23 
                 9.01 
                 8.56 
                 6.39 
               
               
                 SG461 
                 5.73 
                 6.16 
                 6.23 
                 6.38 
                 6.72 
                 6.01 
                 6.39 
                 7.02 
                 7.05 
                 5.73 
               
               
                 SG493 
                 6.78 
                 7.05 
                 5.03 
                 5.15 
                 6.95 
                 6.37 
                 6.22 
                 7.87 
                 8.07 
                 6.78 
               
               
                 SG507 
                 7.83 
                 7.62 
                 5.83 
                 5.78 
                 8.17 
                 7.26 
                 7.85 
                 9.74 
                 8.82 
                 7.83 
               
               
                 SG508 
                 6.42 
                 6.46 
                 6.90 
                 4.56 
                 6.62 
                 6.70 
                 6.71 
                 8.19 
                 8.17 
                 6.42 
               
               
                 x i   
                 −107.44 
                 −99.01 
                 −48.21 
                 −172.85 
                 −40.21 
                 −93.50 
                 −56.20 
                 85.27 
                 64.43 
                 −107.44 
               
               
                 p i   
                 0.00 
                 0.00 
                 0.00 
                 0.00 
                 0.00 
                 0.00 
                 0.00 
                 1.00 
                 1.00 
                 0.00 
               
               
                   
               
             
          
           
               
                 lmn i   
                 CLL148b.10 
                 CLL148c.11 
                 CLL111.12 
                 CLL163.13 
                 CLL108.15 
                 CLL160.1 
                 CLL160.2 
                 CL L187.5 
               
               
                   
               
               
                 SG117 
                 6.98 
                 6.83 
                 6.54 
                 6.16 
                 6.87 
                 7.74 
                 7.71 
                 7.58 
               
               
                 SG428 
                 6.64 
                 6.63 
                 6.17 
                 5.61 
                 6.56 
                 5.92 
                 5.69 
                 7.24 
               
               
                 SG459 
                 9.13 
                 9.29 
                 8.44 
                 8.33 
                 8.55 
                 8.29 
                 8.25 
                 9.01 
               
               
                 SG461 
                 7.16 
                 7.48 
                 6.67 
                 6.61 
                 6.86 
                 7.21 
                 7.25 
                 7.35 
               
               
                 SG493 
                 7.70 
                 7.89 
                 8.05 
                 7.92 
                 7.67 
                 7.66 
                 7.58 
                 8.05 
               
               
                 SG507 
                 9.90 
                 10.02 
                 9.16 
                 9.16 
                 9.66 
                 8.88 
                 8.93 
                 9.99 
               
               
                 SG508 
                 8.27 
                 8.45 
                 7.92 
                 7.86 
                 7.89 
                 7.57 
                 7.51 
                 8.30 
               
               
                 x i   
                 102.70 
                 125.01 
                 39.43 
                 28.30 
                 58.29 
                 51.63 
                 48.76 
                 109.23 
               
               
                 p i   
                 1.00 
                 1.00 
                 1.00 
                 1.00 
                 1.00 
                 1.00 
                 1.00 
                 1.00 
               
               
                   
               
             
          
           
               
                 lmn i   
                 CLL197.14 
                 CLL198.15 
                 CLL199.16 
                 CLL200.17 
                 CLL201.18 
                 CLL20_LE 
                 CLL208.1 
                 CLL210.2 
               
               
                   
               
               
                 SG117 
                 6.66 
                 6.13 
                 7.14 
                 7.58 
                 7.97 
                 6.67 
                 7.40 
                 7.11 
               
               
                 SG428 
                 5.98 
                 5.10 
                 6.71 
                 6.72 
                 7.54 
                 5.97 
                 6.77 
                 6.71 
               
               
                 SG459 
                 8.35 
                 7.97 
                 8.34 
                 8.99 
                 9.30 
                 8.26 
                 8.34 
                 8.19 
               
               
                 SG461 
                 6.76 
                 6.36 
                 7.02 
                 7.26 
                 7.35 
                 6.83 
                 6.99 
                 6.79 
               
               
                 SG493 
                 7.80 
                 7.27 
                 7.96 
                 8.09 
                 8.39 
                 7.53 
                 7.44 
                 7.48 
               
               
                 SG507 
                 9.38 
                 8.71 
                 9.58 
                 9.87 
                 10.23 
                 9.04 
                 8.65 
                 9.26 
               
               
                 SG508 
                 8.00 
                 7.48 
                 7.72 
                 8.64 
                 8.76 
                 7.17 
                 7.09 
                 7.61 
               
               
                 x i   
                 48.40 
                 0.40 
                 48.33 
                 116.75 
                 134.69 
                 14.31 
                 29.64 
                 39.38 
               
               
                 p i   
                 1.00 
                 0.60 
                 1.00 
                 1.00 
                 1.00 
                 1.00 
                 1.00 
                 1.00 
               
               
                   
               
             
          
           
               
                 lmn i   
                 CLL225.6 
                 CLL236.7 
                 CLL240.8 
                 CLL184b.9 
                 CLL184C.10 
                 CLL208.1 
                 CLL213.5 
                 CLL214.6 
               
               
                   
               
               
                 SG117 
                 7.35 
                 6.54 
                 6.80 
                 7.12 
                 7.06 
                 7.24 
                 6.97 
                 7.06 
               
               
                 SG428 
                 6.46 
                 6.43 
                 6.11 
                 6.97 
                 6.36 
                 6.34 
                 5.80 
                 6.45 
               
               
                 SG459 
                 8.20 
                 7.60 
                 8.24 
                 8.37 
                 8.37 
                 8.07 
                 8.17 
                 8.35 
               
               
                 SG461 
                 6.90 
                 6.85 
                 6.58 
                 7.05 
                 6.73 
                 6.53 
                 6.43 
                 6.79 
               
               
                 SG493 
                 7.28 
                 6.90 
                 6.77 
                 7.40 
                 7.17 
                 7.59 
                 7.47 
                 7.63 
               
               
                 SG507 
                 8.45 
                 8.55 
                 8.85 
                 9.22 
                 8.88 
                 8.08 
                 8.61 
                 9.13 
               
               
                 SG508 
                 7.13 
                 7.29 
                 6.93 
                 8.21 
                 8.01 
                 7.14 
                 7.77 
                 7.72 
               
               
                 x i   
                 25.36 
                 22.47 
                 7.52 
                 88.13 
                 65.29 
                 0.80 
                 26.04 
                 44.00 
               
               
                 p i   
                 1.00 
                 1.00 
                 1.00 
                 1.00 
                 1.00 
                 0.69 
                 1.00 
                 1.00 
               
               
                   
               
             
          
           
               
                 lmn i   
                 CLL221.7 
                 CLL193.1 
                 CLL193.2 
                 CLL197.1 
                 CLL197.2 
               
               
                   
               
               
                 SG117 
                 6.97 
                 6.76 
                 6.73 
                 6.22 
                 6.00 
               
               
                 SG428 
                 6.47 
                 7.26 
                 7.22 
                 5.81 
                 5.71 
               
               
                 SG459 
                 7.98 
                 8.28 
                 8.27 
                 8.26 
                 8.07 
               
               
                 SG461 
                 6.60 
                 7.18 
                 7.17 
                 6.78 
                 6.62 
               
               
                 SG493 
                 7.66 
                 7.95 
                 7.93 
                 7.79 
                 7.85 
               
               
                 SG507 
                 9.23 
                 9.01 
                 9.04 
                 8.86 
                 8.72 
               
               
                 SG508 
                 7.74 
                 7.68 
                 7.77 
                 7.55 
                 7.64 
               
               
                 x i   
                 27.46 
                 56.71 
                 60.37 
                 23.63 
                 14.87 
               
               
                 p i   
                 1.00 
                 1.00 
                 1.00 
                 1.00 
                 1.00 
               
               
                   
               
             
          
         
       
     
       Example 5 
     Results Obtained with “Stable” CLL Samples Compared with “Progressive” CLL Samples 
       [0257]    “CLL-stable type” (S) samples are considered those of patients who have had stable CLL for over 5 years and “CLL-progressive type” (P) samples are considered the samples of patients classified as stable at the time of diagnosis and whose disease has progressed in less than one year. 
         [0258]    In total 6 S samples and 6 P samples were analysed. The 12 samples were collected at the time of diagnosis, without clinical differences between them, but after one year, 6 of those patients had progressed. The 12 hybridizations have passed the aforementioned quality criteria. 
         [0259]    Stable samples: E142R, E148, E156, E163, E164, E193 
         [0260]    Progressive samples: P111, P105, P177, P158, P157 and P197. 
         [0261]    All the data analysis was performed in R version 1.9.1. 
         [0262]    Data normalization. In this case, and to avoid the significant genes obtained are due to a real difference between samples and not to the effect of normalization, the data were normalized in two different forms (“variance stabilization normalization” (vsn) and by robust quantiles) and the same statistical analysis was performed with each one of the normalizations.
       Statistical analysis with normalized data by “variance stabilization normalization”. The list of statistically significant genes was obtained from a Welch&#39;s test with the mt.maxT function of the multtest package in R, with a value of p&lt;0.05 without adjusting, i.e. without performing any control on the false positives and produced a list of 29 genes with stat istically significant differences between the CLL-stable type and CLL-progressive type groups.       
 
         [0264]    The statistically significant oligonucleotides obtained were: 
         [0000]    SG26, SG31, SG70, SG98, SG177, SG194, SG195, SG208, SG213, SG216, SG272, SG293, SG301, SG309, SG321, SG333, SG343, SG352, SG357, SG366, SG368, SG405, SG426, SG439, SG447, SG452, SG521, SG555, SG556. 
         [0265]    The samples were grouped, which was performed with the hclust function of the stats package in R applying Pearson correlations. The tree obtained is shown in part A of  FIG. 4 . 
         [0266]    The hierarchical grouping of the 12 samples in accordance with the expression of the 29 statistically significant genes obtained grouped the samples correctly: the tree contains two large branches, of which the right branch contains the 6 stable samples and the left branch contains the 6 progressive samples.
       Statistical analysis with normalized data by robust quantiles The list of statistically significant genes was obtained from a Welch&#39;s test with the mt.maxT function of the multtest package in R with the values of p without adjusting i.e. without exerting any control over the rate of false positives, with a value of p&lt;0.05, and produced a list of 19 genes with statistically significant differences between the CLL-stable type and CLL-progressive type groups:   SG26, SG31, SG177, SG194, SG195, SG197, SG213, SG216, SG293, SG301, SG309, SG333, SG343, SG357, SG366, SG439, SG452, SG555, SG556.       
 
         [0269]    The supervised grouping of the 12 samples in accordance with the expression of the 19 statistically significant genes obtained gave rise to the tree which appears in part B of  FIG. 4 , wherein the samples also appear correctly grouped. 
         [0270]    18 oligonucleotides common to both lists of statistically significant genes were selected and the average intensity of each one of them in the group of stable samples and in the group of progressive samples was calculated, as well as the variation in average intensity between the stable and progressive groups. 
         [0271]    The values obtained are shown in Table 14. 
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 14 
               
             
             
               
                   
               
               
                 Values corresponding to the intensity of 18 significant oligonucleotides 
               
               
                 to distinguish between CLL-stable and CLL-progressive 
               
             
          
           
               
                   
                 Stable CLL 
                 Progressive CLL 
                 Change 
               
               
                   
                 group 
                 group 
                 stable/ 
               
             
          
           
               
                   
                 Significance 
                 Average 
                   
                 Average 
                   
                 progres- 
               
               
                 Probe 
                 (p data vsn) 
                 Intensity 
                 SD 
                 Intensity 
                 SD 
                 sive 
               
               
                   
               
             
          
           
               
                 SG177 
                 0.001 
                 14 
                 1.71 
                 21 
                 4.84 
                 0.7 
               
               
                 SG366 
                 0.001 
                 18 
                 2.33 
                 14 
                 1.80 
                 1.3 
               
               
                 SG309 
                 0.004 
                 20 
                 2.76 
                 15 
                 3.58 
                 1.4 
               
               
                 SG26 
                 0.005 
                 97 
                 19.20 
                 70, 
                 13.24 
                 1.4 
               
               
                 SG452 
                 0.010 
                 16 
                 2.19 
                 12 
                 3.08 
                 1.3 
               
               
                 SG216 
                 0.012 
                 46 
                 14.64 
                 31 
                 7.13 
                 1.5 
               
               
                 SG333 
                 0.013 
                 36 
                 7.28 
                 53 
                 16.25 
                 0.7 
               
               
                 SG357 
                 0.014 
                 134 
                 6.50 
                 175 
                 38.67 
                 0.8 
               
               
                 SG213 
                 0.014 
                 26 
                 5.51 
                 41 
                 17.20 
                 0.6 
               
               
                 SG31 
                 0.014 
                 69 
                 32.50 
                 30 
                 10.57 
                 1.8 
               
               
                 SG301 
                 0.014 
                 21 
                 5.02 
                 16 
                 3.10 
                 1.4 
               
               
                 SG194 
                 0.019 
                 37 
                 9.52 
                 50 
                 9.95 
                 0.7 
               
               
                 SG456 
                 0.022 
                 11 
                 2.06 
                 14 
                 2.08 
                 0.8 
               
               
                 SG293 
                 0.029 
                 17 
                 1.88 
                 21 
                 3.72 
                 0.8 
               
               
                 SG343 
                 0.033 
                 27 
                 7.43 
                 21 
                 1.61 
                 1.3 
               
               
                 SG439 
                 0.038 
                 18 
                 2.00 
                 20 
                 1.74 
                 0.9 
               
               
                 SG195 
                 0.041 
                 21 
                 3.56 
                 25, 
                 4.60 
                 0.8 
               
               
                 SG555 
                 0.049 
                 163 
                 23.55 
                 137 
                 20.69 
                 1.2 
               
               
                   
               
             
          
         
       
     
         [0272]    To validate the results obtained with the microarray, 5 of the common statistically significant probes were selected obtained on comparing expression data from stable CLL subjects compared to progressive CLL subjects and the expression was studied with RT-PCR of the genes represented by those probes. The criteria used to select the 5 probes were: hybridization intensity, change of intensity between groups of stable and progressive and value of statistical significance. In this way, 5 probes were selected which represent genes PSMB4, CD23A, LCP1, ABCC5 and POU2F2. The expression of these 5 genes was determined in 11 of the 12 CLL type samples, as there was no total RNA of sample 105. With the expression value of the genes in each sample, the rate of change was determined between the group of stable and progressive and the value of significance of that variation and it was compared with the results obtained with the microarrays. 
         [0273]    The technique used for the validation was RT-PCR or PCR in real time using a LightCycler. This technique is the technique of choice to validate data chips and as with the microarrays, measures mRNA level. 
         [0274]    Primers were designed for each one of the 5 genes whose representative oligonucleotide was selected. The details thereof are shown below in Table 15. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 15 
               
             
             
               
                   
               
               
                 Primers and amplification products of the genes selected  
               
               
                 for their validation by RT-PCR 
               
             
          
           
               
                   
                   
                   
                 Amplified 
                   
               
               
                   
                   
                   
                 product 
                   
               
               
                 Gene 
                 Primer sequences (5′-3′) 
                 SEQ ID NO: 
                 size 
                 T m   
               
               
                   
               
               
                 PSMB4 
                 Direct: PSMB4_F 
                 SEQ ID NO: 598 
                 95 pb 
                 81° C. 
               
               
                   
                 TTCTGGGAGATGGACACAGCTATA 
                   
                   
                   
               
               
                   
                 Inverse: PSMB4_R 
                 SEQ ID NO: 599 
                   
                   
               
               
                   
                 CCACAAAGGGTTCATCTTCGA 
                   
                   
                   
               
               
                   
               
               
                 CD23A 
                 Direct: CD23A_F 
                 SEQ ID NO: 600 
                 97 pb 
                 82° C. 
               
               
                   
                 TGCCCTGAAAAGTGGATCAAT 
                   
                   
                   
               
               
                   
                 Reverse: CD23A_R 
                 SEQ ID NO: 601 
                   
                   
               
               
                   
                 CCATGTCGTCACAGGCATACC 
                   
                   
                   
               
               
                   
               
               
                 LCP1 
                 Direct: LCP1_F 
                 SEQ ID NO: 602 
                 126 pb 
                 77° C. 
               
               
                   
                 CCAGGTACCCTTCTCGCTTTT 
                   
                   
                   
               
               
                   
                 Reverse: LCP1_R 
                 SEQ ID NO: 603 
                   
                   
               
               
                   
                 CTCCTGGCCCTCATCTTGAA 
                   
                   
                   
               
               
                   
               
               
                 ABCC5 
                 Direct: ABCC5_F 
                 SEQ ID NO: 604 
                 119 pb 
                 82° C. 
               
               
                   
                 CCCTCAAAGTCTGCAACTTTAAGC 
                   
                   
                   
               
               
                   
                 Reverse: ABCC5_R 
                 SEQ ID NO: 605 
                   
                   
               
               
                   
                 ACACACCAAACCACACAGCAA 
                   
                   
                   
               
               
                   
               
               
                 POU2F2 
                 Direct: POU2F2_F 
                 SEQ ID NO: 606 
                 136 pb 
                 82° C. 
               
               
                   
                 GAGGACCAGCATCGAGACAAA 
                   
                   
                   
               
               
                   
                 Reverse: POU2F2_R 
                 SEQ ID NO: 607 
                   
                   
               
               
                   
                 AACCAGACGCGGATCACTTC 
               
               
                   
               
             
          
         
       
     
         [0275]      FIG. 5  shows the distribution of the expression data obtained by RT-PCR (left graphic) and by the microarray (right graphic). Part A corresponds to gene PSMB4, part B to gene CD23A and part C to gene POU2F2. 
         [0276]    Below, in Table 16, the results obtained with the microarray and with RT-PCR are obtained of the change values of the 5 genes selected in thr group of stable samples compared with the group of progressive samples obtained as significance of the change. In 3 of the 5 genes selected (PSMB4, CD23A and POU2F2) the values of change, the direction of the change and the significance values obtained with RT-PCR agree with those obtained with the microarray, for which reason those 3 genes are considered valid, i.e. the results obtained for those 3 genes with the microarray coincide with the results obtained by another techniques which also measures mRNA level. 
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 16 
               
             
             
               
                   
               
               
                 Values of change and significance of the change obtained with 
               
               
                 the microarray and by RT-PCR 
               
             
          
           
               
                   
                   
                 Stable/progressive 
                   
               
               
                   
                   
                 change 
                 Significance of the change 
               
             
          
           
               
                 Probes 
                 Genes 
                 Array 
                 RT-PCR 
                 Array 
                 RT-PCR 
               
               
                   
               
             
          
           
               
                 SG26 
                 PSBM4 
                 1.3 
                 1.5 
                 0.04 
                 0.15 
               
               
                 SG216 
                 CD23A 
                 1.5 
                 3.2 
                 0.04 
                 0.03 
               
               
                 SG333 
                 LCP1 
                 0.7 
                 1 
                 0.05 
                 0.97 
               
               
                 SG357 
                 ABCC5 
                 0.8 
                 1.3 
                 0.10 
                 0.28 
               
               
                 SG366 
                 POU2F2 
                 1.3 
                 2.3 
                 0.01 
                 0.05 
               
               
                   
               
             
          
         
       
     
       BIBLIOGRAPHIC REFERENCES 
       [0000]    
       
         Alizadeh A, Eisen M, Davis R E, et al The lymphochip: a specialized cDNA microarray for the genomic-scale analysis of gene expression in normal and malignant lymphocytes. Cold Spring Harb Symp Quant Biol. 1999; 64:71-8. 
         Alizadeh A A, Eisen M B, Davis R E, et al Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000; 403:503-11. 
         Arico M, Valsecchi M G, Camitta B, Schrappe M, Chessells J, Baruchel A, Gaynon P, Silverman L, Janka-Schaub G, Kamps W, Pui C H, Masera G. Outcome of treatment in children with Philadelphia chromosome-positive acute lymphoblastic leukemia N Engl J. Med. 2000; 342:998-1006.). 
         Bea S, Zettl A, Wright G, et al. Diffuse Large B-Cell Lymphoma Subgroups Have Distinct Genetic Profiles that Influence Tumor Biology and Improve Gene Expression-Based Survival Prediction. Blood. 2005 04:-1399 
         Bene M C, Bernier M, Casasnovas R O, et al: Acute myeloid leukaemia M O: Haematological, immunophenotypic and cytogenetic characteristics and their prognostic significance: An analysis in 241 patients. Br J Haemat 113:737, 2001. 
       
     
         [0282]    Benes V, Muckenthaler M. Standardization of protocols in cDNA microarray analysis. Trends Biochem Sci. 2003; 28:244-9
   Bennett J M, Catovsky D, Daniel M T, et al. Myelodysplastic syndromes: is another classification necessary? Br J. Haematol. 1984; 56:515-7.   Bennett J M, Catovsky D, Daniel M T, et al. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J. Haematol. 1976; 33:451-8.   Bergh G, Ehinger M, Olsson I, Jacobsen S E, Gullberg U. Involvement of the retinoblastoma protein in monocytic and neutrophilic lineage commitment of human bone marrow progenitor cells Blood. 1999; 94:1971-8   Bernard J, Levy J P, Varet B. Hematologie. Collection Medico Chirurgicale. Paris: Flammarion, 1976; 5-22   Binet J L, Auquier A, Dighiero G, et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer. 1981; 48:198-206   Boultwood J, Lewis S, Wainscoat J S The 5q-syndrome. Blood. 1994; 84:3253-60   Braziel R M, Shipp M A, Feldman A L, et al. Molecular diagnostics. Hematology (Am Soc Hematol Educ Program). 2003; 279-93   Bullinger, Milner et al. Use of gene-expression profiling to identify prognostic subclasses in adult acute myeloid leukemia N Engl Med 2005; 350:1605-16   Chan W C. Gene expression profiling in lymphoma diagnosis and research. Croat Med J. 2005; 46:349-59   Chen C C, Andrich M P, Metcalfe D D: A retrospective analysis of bone scan abnormalities in mastocytosis: Correlation with disease category and prognosis. J Nucl Med 35:1471, 1994   Cossman J: Gene expression analysis of single neoplastic cells and the pathogenesis of Hodgkin&#39;s lymphoma. J Histochem Cytochem 2001; 49:799-800   Crespo M, Bosch F, Villamor N, et al. ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J. Med. 2003; 348:1764-75   Datta S R, Brunet A, Greenberg M E. Cellular survival: A play in three acts. Genes Dev 1999; 13: 2905-2927   Devilard E, Bertucci F, Tremat P, et al: Gene expression profiling defines molecular subtypes of classical Hodgkin&#39;s lymphoma. Oncogene 2002; 21:3095-3102   Dohner K, Tobis K, Ulrich R, Frohling S, Benner A, Schlenk R F, Dohner H. Prognostic significance of partial tandem duplications of the MLL gene in adult patients 16 to 60 years old with acute myeloid leukemia and normal cytogenetics: a study of the Acute Myeloid Leukemia Study Group Ulm. J Clin Oncol. 2002; 20:3254-61   Domen J, Weissman I L. Self-renewal, differentiation or death: regulation and manipulation of hematopoietic stem cell fate. Mol Med. Today. 1999; 5:201-8   Durig J, Naschar M, Schmucker U, Renzing-Kohler K, Holter T, Huttmann A, Duhrsen U. CD38 expression is an important prognostic marker in chronic lymphocytic leukaemia. Leukemia. 2002; 16:30-5   Ferrando A A, Look A T Pathobiology of acute lymphoblastic leukemia. In Hoffman R Hematology Basic Principles and practice. 4 ed. Churchill Livingstone New York 2005; 1135-1147   Galton D A. The pathogenesis of chronic lymphocytic leukemia Can Med Assoc J. 1966; 94:1005-10   Giles F J, Keating A, Goldstone A H, Avivi I, Willman C L, Kantarjian H M Acute myeloid leukemia. Hematology (Am Soc Hematol Educ Program). 2002; 73-110.).   Golub T R, Slonim D K, Tamayo P, et al. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science. 1999; 286:531-7   Gong J Z, Lagoo A S, Peters D, Horvatinovich J, Benz P, Buckley P J. Value of CD23 determination by flow cytometry in differentiating mantle cell lymphoma from chronic lymphocytic leukemia/small lymphocytic lymphoma Am J Clin Pathol. 2001; 116:893-7   Greiner TC.mRNA microarray analysis in lymphoma and leukemia. Cancer Treat Res. 2004; 121:1-12   Guttmacher A E, Collins F S. Welcome to the genomic era N Engl J. Med. 2003; 349:996-8   Hamblin T J, Davis Z, Gardiner A, Oscier D G, Stevenson F K Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood. 1999; 94:1848-54   Hanahan D, Weinberg R A: The hallmarks of cancer. Cell 100:57-70, 2000   Harris N L, Jaffe E S, Diebold J, et al. The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November, 1997 Ann Oncol. 1999; 10:1419-32   Harris N L, Jaffe E S, Diebold J, et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November 1997 J Clin Oncol. 1999; 17:3835-49   Harris N L, Jaffe E S, Stein H, et al A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group Blood. 1994; 84:1361-92   Harris N L, Stein H, Coupland S E, Hummel M, Favera R D, Pasqualucci L, Chan W C New approaches to lymphoma diagnosis. Hematology (Am Soc Hematol Educ Program). 2001; 194-220.   Heaney M L, Golde D W Myelodysplasia. N Engl J. Med. 1999; 340:1649-60   Jaffe E S, Harris N L, Stein H, Vardiman J W. WHO Classification Tumours of Heamotopoietic and lymphoid tissues. En Pathology and Genetics of tumours of Haematopoietic and lymphoid tissues. IARC Press. Lyon, 2001.   Jemal A, Murray T, Samuels A, et al: Cancer statistics, 2003. CA Cancer J Clin 53:5, 2003   Kottaridis P D, Gale R E, Frew M E, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood. 2001; 98:1752-9   Kuppers R, Klein U, Hansmann M L, Rajewsky K. Cellular origin of human B-cell lymphomas. N Engl J. Med. 1999; 341:1520-9   Küppers R: Molecular biology of Hodgkin&#39;s lymphoma. Adv Cancer Res 2002; 84:277-312   Kyle R A: Monoclonal gammopathy of undetermined significance and solitary plasmacytoma: Implications for progression to overt multiple myeloma. Hematol Oncol Clin North Am 11:71, 1997   Lee M F, Dang C V Control of cell division. In Hoffman R Hematology Basic Principles and practice. 4 ed. Churchill Livingstone New York 2005; 69-81   Leung AYH, Verfaillie C M Stem cell model of hematopoyesis. In Hoffman R Hematology Basic Principles and practice. 4 ed. Churchill Livingstone New York 2005; 200-214   Magli M C, Largman C, Lawrence H J Effects of HOX homeobox genes in blood cell differentiation J Cell Physiol. 1997; 173:168-77   Mitelman F, Mertens F, Johansson B A breakpoint map of recurrent chromosomal rearrangements in human neoplasia. Nat. Genet. 1997; 15 Spec No:417-74   Montoto S, Lopez-Guillermo A, Colomer D, et al. Incidence and clinical significance of bcl-2/IgH rearrangements in follicular lymphoma. Leuk Lymphoma. 2003; 44:71-6.   Nichogiannopoulou A, Trevisan M, Friedrich C, Georgopoulos K. Ikaros in hemopoietic lineage determination and homeostasis Semin Immunol. 1998; 10:119-25.   Nutt S L, Heavey B, Rolink A G, Busslinger M. Commitment to the B-lymphoid lineage depends on the transcription factor Pax5. Nature. 1999; 401:556-62   O&#39;Gorman D M, Cotter T G Molecular signals in anti-apoptotic survival pathways. Leukemia. 2001; 15:21-34   Pane F, Intrieri M, Quintarelli C, Izzo B, Muccioli G C, Salvatore F BCR/ABL genes and leukemic phenotype: from molecular mechanisms to clinical correlations. Oncogene. 2002; 21:8652-67.   R Development Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria, 2004   Rai K R, Sawitsky A, Cronkite E P, Chanana A D, Levy R N, Pasternack B S. Clinical staging of chronic lymphocytic leukemia. Blood. 1975; 46:219-34   Roumier C, Eclache V, Imbert M, et al. M O AML, clinical and biologic features of the disease, including AML1 gene mutations: A report of 59 cases by the Groupe Francais d&#39;Hematologie Cellulaire (GFHC) and the Groupe Francais de Bytogenetique Hematologique (GFCH). Blood 101:1277, 2003   Shaffer A L, Rosenwald A, Staudt L M Lymphoid malignancies: the dark side of B-cell differentiation Nat Rev Immunol. 2002; 2:920-32   Tenen D G, Hromas R, Licht J D, Zhang D E Transcription factors, normal myeloid development, and leucemia. Blood. 1997; 90:489-519   Tibshirani R, Hastie T, Narasimhan B, Chu G. Diagnosis of multiple cancer types by shrunken centroids of gene expression. Proc. Natl. Acad. Sci. 2002; 99:6567-72   Vardiman J W, Harris N L, Brunning R D The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002; 100:2292-302   Venables, Smith et al. An Introduction to R, Notes on R: A programming Environment for Data Analysis. 2004   Weissman I L Stem cells: Units of regeneration and units in evolution. Cell, 2000; 100:157-168.   Westbrook C A. The molecular basis of neoplasia. In Hoffman R Hematology Basic Principles and practice. 4 ed. Churchill Livingstone New York 2005; 941-945   Zhan F, Hardin J, Kordsmeier B, et al: Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells. Blood 99:1745, 2002   
 
       BRIEF DESCRIPTION OF THE FIGURES 
       [0340]      FIG. 1  shows the grouping of samples of cells U937 compared with Jurkat cells in accordance with differences in the gene expression between the samples. Part A corresponds to the non-supervised grouping; part B corresponds to the supervised grouping. 
         [0341]      FIG. 2  shows the grouping of samples of healthy subjects compared with U937 and Jurkat cells in accordance with differences in the gene expression between the samples. Part A corresponds to the non-supervised grouping; part B corresponds to the supervised grouping. 
         [0342]      FIG. 3  shows the grouping of samples of patients with chronic lymphatic leukemia compared with U937 and Jurkat cells in accordance with differences in the gene expression between the samples. Part A corresponds to the non-supervised grouping; part B corresponds to the supervised grouping. 
         [0343]      FIG. 4  shows the grouping of samples of patients with “stable” chronic lymphatic leukemia compared with samples of patients with “progressive” chronic lymphatic leukemia in accordance with differences in gene expression. Part A corresponds to the grouping in accordance with the genes identified as significant after normalization with “vsn” and use of the mt.maxT function in R; part B corresponds to the grouping in accordance with the genes identified as significant after normalization by robust quartiles and use of the mt.maxT function in R. 
         [0344]      FIG. 5  shows the distribution of the expression data obtained by RT-PCR (left-hand graphic) and from the intensity values obtained from the microarray (right-hand graphic) for the PSMB4 genes (part A: upper graphic), CD23A (part B: intermediate graphic) and POU2F2 (part C: lower graphics) in samples of patients with “stable” chronic lymphatic leukemia (bars marked with “E”) and in samples of patients with “progressive” chronic lymphatic leukemia (bars marked with “P”).