bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of chimeric BCR-ABL genes on bone marrow samples and blood smears in chronic myeloid and acute lymphoblastic leukemia by in situ hybridization
Authors: Bentz M , Cabot G , Moos M , Speicher MR , Ganser A , Lichter P , Dohner H 
Published: October 2019

Abstract
The presence of BCR-ABL fusion genes has important diagnostic and prognostic implications in chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). The CML-specific chimeric BCR-ABL gene with a break involving the major breakpoint cluster region (M-bcr) of the BCR-gene has been detected by means of fluorescence in situ hybridization (FISH). In this study, we present a FISH protocol that allows the detection of breaks in both the major and the minor breakpoint cluster region (m-bcr). Three hybridization signals of D107F9, a yeast artificial chromosome (YAC)-derived probe spanning the breakpoint regions of the BCR gene, were indicative of the translocation events. To increase the specificity further, this probe was combined with cos-abl 8, a cosmid probe flanking the breakpoint within the ABL gene for dual-color hybridization. Samples of 21 patients with CML, the ALL-derived cell line SUP-B15, and of seven patients with Philadelphia chromosome (Ph1)-positive ALL (three of them with breakpoints within m-bcr) were examined. BCR-ABL fusion was detected in all cases with high specificity (false-positive nuclei: mean, 0.1%). On cytogenetic preparations, the percentages of BCR-ABL- positive interphase cells ranged from 53% to 91%. Comparable efficiencies were achieved on blood smears. In conclusion, hybridization with D107F9 and cos-abl 8 allows unambiguous diagnosis of BCR-ABL genes and is likely to become an important tool for the monitoring of therapies in patients with CML and ALL.
Recovery of HLA-restricted cytomegalovirus (CMV)-specific T-cell responses after allogeneic bone marrow transplant: correlation with CMV disease and effect of ganciclovir prophylaxis
Authors: Li CR , Greenberg PD , Gilbert MJ , Goodrich JM , Riddell SR 
Published: October 2019

Abstract
Protection from cytomegalovirus (CMV) disease in immunocompromised hosts has been shown to correlate with recovery of the host virus- specific CD8+ T-cell response. The administration of ganciclovir to immunosuppressed transplant recipients as antiviral prophylaxis has reduced the early risk of CMV disease, but late disease is observed with increased frequency, suggesting that recovery of the CMV-specific T-cell responses necessary for protective immunity may be delayed in these patients. Therefore, we evaluated reconstitution of CMV-specific T-cell responses in 47 bone marrow transplant (BMT) recipients entered on a randomized placebo-controlled study of ganciclovir. The study drug was initiated at a mean of 24 days after BMT. At day 30 to 40, a minority of patients had recovery of T-cell immunity to CMV and the frequency of reconstitution was equivalent in patients randomized to ganciclovir or placebo. The failure of ganciclovir to effect early reconstitution may reflect the short duration of treatment. Early recovery was associated with the infusion of BM from a CMV seropositive donor (P = .07 for CD8+ cytotoxic T cell (CTL), P = .04 for CD4+ Th). Between day 40 and day 90, recovery of deficient CD8+ and CD4+ CMV- specific T-cell responses occurred in the majority of individuals that received placebo, but in a minority of ganciclovir recipients. Two cases of late-onset CMV disease occurred in ganciclovir recipients. In all patients, the presence of a CTL response to CMV conferred protection from subsequent CMV disease (P = .005), and these protective CTL responses are shown to be specific for structural virion proteins similar to the responses in immunocompetent CMV seropositive individuals. These data confirm the importance of CMV-specific T-cell responses and suggest that a delay in recovery of these responses as a result of ganciclovir prophylaxis may contribute to the occurrence of late CMV disease.
A human homologue of the Drosophila developmental gene, Notch, is expressed in CD34+ hematopoietic precursors
Authors: Milner LA , Kopan R , Martin DI , Bernstein ID 
Published: October 2019

Abstract
Members of the Notch gene family have been shown to mediate cell-fate decisions by multipotent precursors in a number of different systems. To determine whether members of this family might play a similar role in hematopoiesis, we asked if homologues of the Notch gene are expressed in human hematopoietic precursors. Using degenerate oligonucleotides corresponding to conserved amino acid sequences in known Notch homologues as primers for the polymerase chain reaction (PCR), we demonstrated that at least one Notch homologue is expressed in human bone marrow CD34+ cells, a population enriched for hematopoietic precursors. Cloning and sequencing of the PCR products identified this Notch homologue as TAN-1, a member of the Notch family previously cloned from a T-cell leukemia with a translocation involving this gene. Subsequent evaluation of bone marrow hematopoietic cells for TAN-1 expression using a reverse transcription-PCR assay confirmed the expression of TAN-1 in CD34+ hematopoietic precursors, including the immature subset that lacks expression of lineage-associated antigens (CD34+lin-). These findings, together with the known role of Notch homologues in other systems, suggest that members of the Notch family, including TAN-1, may be involved in mediating cell-fate decisions during hematopoiesis.
The human myeloid cell nuclear differentiation antigen gene is one of at least two related interferon-inducible genes located on chromosome 1q that are expressed specifically in hematopoietic cells
Authors: Briggs RC , Briggs JA , Ozer J , Sealy L , Dworkin LL , Kingsmore SF , Seldin MF , Kaur GP , Athwal RS , Dessypris EN 
Published: October 2019

Abstract
We have previously shown that the human myeloid cell nuclear differentiation antigen (MNDA) is expressed at both the antigen and mRNA levels specifically in human monocytes and granulocytes and earlier stage cells in the myeloid lineage. A 200 amino acid region of the MNDA is strikingly similar to a region in the proteins encoded by a family of interferon-inducible mouse genes, designated Ifi-201, Ifi- 202, Ifi-203, etc, that are not regulated in a cell- or tissue-specific fashion. However, a new member of the Ifi-200 gene family, D3, is induced in mouse mononuclear phagocytes but not in fibroblasts by interferon. The same 200 amino acid region, duplicated in the mouse Ifi- 200 gene family, is also repeated in the recently characterized human IFI 16 gene that is constitutively expressed specifically in lymphoid cells and is induced in myeloid cells by interferon gamma. The 1.8-kb MNDA mRNA, which contains an interferon-stimulated response element in the 5′ untranslated region, was significantly upregulated in human monocytes exposed to interferon alpha. Characterization of the MNDA gene showed that it is a single-copy gene and localized to human chromosome 1q 21–22 within the large linkage group conserved between mouse and human that contains the Ifi-200 gene family. The IFI 16 gene is also located on human chromosome 1q. Our observations are consistent with the proposal that the MNDA is a member of a cluster of related human interferon-regulated genes, similar to the mouse Ifi-200 gene family. In addition, one mouse gene in the Ifi-200 gene family and the human MNDA and IFI 16 genes show expression and/or regulation restricted to cells of the hematopoietic system, suggesting that these genes participate in blood cell-specific responses to interferons.
Cytogenetic features of infants less than 12 months of age at diagnosis of acute lymphoblastic leukemia: impact of the 11q23 breakpoint on outcome: a report of the Childrens Cancer Group
Authors: Heerema NA , Arthur DC , Sather H , Albo V , Feusner J , Lange BJ , Steinherz PG , Zeltzer P , Hammond D , Reaman GH 
Published: October 2019

Abstract
Cytogenetic analyses of pretreatment bone marrows were performed at local institutions as part of Childrens Cancer Group (CCG) protocol CCG- 107 for infants less than 1 year of age with previously untreated acute lymphoblastic leukemia (ALL). Cytogenetic analyses from 39 patients (17 males and 22 females) were accepted after review. Several unique cytogenetic features were observed. Twelve patients (31%) had a t(4;11)(q21;q23) and had a significantly shorter event-free survival (EFS) than did the other patients with adequate cytogenetic analyses (P = .009). Five additional patients had an 11q23 breakpoint, not associated with 4q21. When EFS for these 5 patients was compared with that of the t(4;11) patients, even with these small numbers there was a strong, although not significant, suggestion that the t(4;11) patients have a reduced EFS (P = .09), indicating that the specific translocation, t(4;11)(q21;q23), and not an 11q23 breakpoint per se, may be associated with the poor prognosis of these infants. Structural abnormalities were present in 27 of 28 patients with abnormal karyotypes. A new recurring abnormality, t(5;15)(p15:1;q11) or t(5;15)(p15.3;q13), was identified in 3 patients (Arthur et al, Blood 70:274a, 1987 [abstr, suppl 1]). Two females had structural abnormalities involving Xp11, a breakpoint rarely seen in ALL. Fourteen (36%) patients had a single structural abnormality, and 13 (33%) had complex karyotypes. No patients had hyperdiploidy with more than 50 chromosomes. Only normal chromosomes were observed in 11 patients (28%), and their outcome did not differ from patients with abnormal karyotypes. These cytogenetic abnormalities found in the leukemic cells of infants are clearly different from those in older children and adults, and may explain, in part, the unique biologic characteristics of infant ALL.
LAZ3 rearrangements in non-Hodgkin's lymphoma: correlation with histology, immunophenotype, karyotype, and clinical outcome in 217 patients
Authors: Bastard C , Deweindt C , Kerckaert JP , Lenormand B , Rossi A , Pezzella F , Fruchart C , Duval C , Monconduit M , Tilly H 
Published: October 2019

Abstract
We have recently shown that an evolutionary conserved gene LAZ3, encoding a zinc finger protein, is disrupted and overexpressed in some B-cell lymphomas (mainly with a large cell component) that show chromosomal rearrangements involving 3q27. Because the breakpoints involved in these rearrangements are focused in a narrow major translocation cluster (MTC) on chromosome 3, we used genomic probes from this region to study the molecular rearrangements of LAZ3 in a large series of patients (217) with non-Hodgkin's lymphoma (NHL). Southern blot analysis showed LAZ3 rearrangement in 43 patients (19.8%). Rearrangement was found in 11 of the 84 patients (13%) with follicular lymphoma but was most frequent in aggressive lymphoma (diffuse mixed, diffuse large cell, and large cell immunoblastic subtypes), in which 31 of the 114 patients (27%) were affected. The highest proportion of LAZ3 alteration was observed in B-cell aggressive lymphoma (26 of 71 cases, 37%). Eleven of the 32 patients with 3q27 chromosomal abnormality had no LAZ3 rearrangement, suggesting the possibility of LAZ3 involvement outside the MTC. On the other hand, 18 of the 39 patients with LAZ3 rearrangement and available cytogenetic results did not have visible chromosomal break at 3q27, suggesting that almost a half of the rearrangements are not detectable by cytogenetic methods. No statistical association could be found between LAZ3 status and initial features of the disease or clinical outcome in either follicular or aggressive lymphomas. We conclude that LAZ3 alteration is a relatively frequent event in B-cell lymphoma, especially in those of aggressive histology. It could be used as a genomic marker of the disease, and further studies are needed to clarify clinical implications of these alterations.
Alteration of fibrin network by activated protein C
Authors: Gruber A , Mori E , del Zoppo GJ , Waxman L , Griffin JH 
Published: October 2019

Abstract
The antithrombotic plasma enzyme, activated protein C (APC), may play a role in thrombolysis. In vitro, acceleration of clot lysis by APC depends on its ability to inhibit the activation of prothrombin. The effect of APC on the assembly and dispersion of fibrin network was studied using turbidimetry, plasmin digestion of fibrin, and electron microscopy of plasma clots. The addition of APC before clotting but not after clotting accelerated clot lysis. The rate of increase in the turbidity of clotting plasma was reduced by APC. The turbidity of plasma clots containing APC was directly related to the clot lysis time. Fibrin from plasma clots that were formed in the presence of APC yielded less fibrin degradation products than fibrin from clots without added APC. Furthermore, APC reduced the diameter and relative number of fibrin fibers in plasma clots during gel assembly. We propose that APC may enhance the efficacy of thrombolysis by reducing the relative mass of fibrin within maturing thrombi.
Hairy cell leukemia is characterized by clonal chromosome abnormalities clustered to specific regions
Authors: Haglund U , Juliusson G , Stellan B , Gahrton G 
Published: October 2019

Abstract
Cytogenetic analysis was performed on B-cell mitogen-stimulated cells from 36 patients with symptomatic hairy cell leukemia. Evaluable metaphases were achieved from 30 patients, and (67%) showed clonal abnormalities. Recurrent chromosomal aberrations involving chromosomes 1, 2, 5, 6, 11, 19, and 20 were found. The abnormalities were mostly deletions and inversions, whereas translocations and numerical abnormalities, except trisomy 5, were rare. Fourteen patients showed multiple clones, which mostly were unrelated and found in different combinations in individual cells. Cells with non-clonal abnormalities identical to those found in clonal changes in other patients were common. Chromosome 5 was involved in clonal aberrations in 12 of 30 (40%) patients, most commonly as trisomy 5 (n = 4), or pericentric inversions (n = 6) and interstitial deletions (n = 4) involving band 5q13. Three patients showed two and 1 patient three different clones that involved chromosome 5. In addition, 1 patient had a rare constitutional inversion of chromosome 5 with breakpoints at p13.1 and q13.3. Pericentric inversions and interstitial deletions of chromosome 2 occurred clonally in 4 patients (13%) and in single cells of another 6 patients. Deletions of chromosome 1 at band q42 was found in 5 patients, and 1 patient had a translocation between 1q42 and a supernumerary chromosome 5. Deletions of 6q and 11q were similar to those commonly found in other lymphoproliferative disorders. Trisomy 5, structural abnormalities involving the pericentromeric regions of chromosomes 5 and 2, and 1q42 abnormalities were findings distinguishing the karyotypes in hairy cell leukemia from those of other hematologic malignancies.
Membrane-associated forms of the beta A4 amyloid protein precursor of Alzheimer's disease in human platelet and brain: surface expression on the activated human platelet
Authors: Li QX , Berndt MC , Bush AI , Rumble B , Mackenzie I , Friedhuber A , Beyreuther K , Masters CL 
Published: October 2019

Abstract
The amyloid protein precursor (APP) of Alzheimer's disease (AD) is abundantly expressed in platelets, where its primary function remains undetermined. As an integral transmembrane protein, the release of APP from the membrane may be a critical event in AD. We examined the association of APP with human platelet membranes using a combination of alkali treatment and immunoprecipitation of the carboxyl-terminus of APP. Most of the platelet membrane-associated APP (APPMem) with molecular mass of 100 to 130 kD is removed with alkali treatment and is also truncated at the carboxyl-terminus. APPMem is present at least in part on the surface of the platelet. The full-length transmembrane form of APP, as a 140- to 150-kD minor species, is alkali resistant and is also present on the plasma membrane. In contrast, most of the APPMem from brain is full-length (possessing the carboxyl-terminus) with a molecular mass of 105 to 130 kD and is resistant to alkali treatment. Immunoelectron microscopy shows platelet APP to be localized to the alpha-granule. Activation of platelets results in a threefold increase in surface APP detectability. In plasma, the 130-kD APP-reactive band is increased in AD. We find that in the gray platelet syndrome, platelets contain reduced amounts of APP, with a corresponding reduction in plasma APP levels, suggesting that platelets are the major source of plasma APP. Our studies also identify an interaction of APP with platelet membranes which differs from that found in the brain, and raise the possibility of a receptor for APP in platelet membranes. Quantitative differences in the amounts of APPMem in platelets compared with brain also indicate regulation of the pathways that determine the cleavage of APP near its transmembrane domain. These pathways are a therapeutic target in AD, and may be easily amenable to investigation in platelets.
Cytokine gene expression in B-cell chronic lymphocytic leukemia: evidence of constitutive interleukin-8 (IL-8) mRNA expression and secretion of biologically active IL-8 protein
Authors: di Celle PF , Carbone A , Marchis D , Zhou D , Sozzani S , Zupo S , Pini M , Mantovani A , Foa R 
Published: October 2019

Abstract
To extent our knowledge on the cytokines possibly involved in the pathophysiology of B-cell chronic lymphocytic leukemia (B-CLL), the mRNA expression of a panel of 10 cytokines was investigated on purified B-CLL cells using a reverse-transcriptase polymerase chain reaction method. Whereas negative RT-PCR signals were recorded for interleukin-1 alpha (IL-1 alpha), IL-2, IL-3, IL-4, IL-5, IL-7, tumor necrosis factor beta (TNF beta), and granulocyte-macrophage colony-stimulating factor, we detected the expression of IL-1 beta, IL-6 and TNF alpha. Furthermore, the constitutive expression of IL-8 mRNA was observed in all 17 B-CLL samples analyzed. mRNA expression was associated with the capacity of the leukemic cells to release IL-8 both constitutively (4.6 +/- 8.1 SD ng/mL) and, to a further extent, after stimulation (14.5 +/- 19.4 ng/mL). The circulating levels of IL-8 were also evaluated in 12 untreated B-CLL sera samples and the overall mean level was significantly higher (P <.01) than in normal sera. In addition, supernatants of purified B-CLL cells cultured in the presence of 12-O- tetradecanoylphorbol-13-acetate showed chemotactic activity towards neutrophils; this activity was neutralized in the presence of an anti- IL-8 antiserum. The mRNA for IL-8 was absent in five B-cell preparations from hairy cell leukemia cases and in four B-cell lines. Normal tonsil CD5+ B cells showed a low expression of IL-8 mRNA only in two of the nine preparations tested and the overall quantity of IL-8 released by these cells after 3 days' incubation was significantly lower compared with that released by B-CLL cells (0.4 +/- 0.3 and 1.6 +/- 0.9 ng/mL under basal and stimulated conditions, respectively). These findings point to an involvement of a member of the proinflammatory chemokine supergene family in human CD5+ B lymphocytes. The different IL-8 behavior observed between B-CLL cells and their normal counterpart is likely to reflect an activation state of the leukemic population.
Mast cell growth factor modulates CD36 antigen expression on erythroid progenitors from human bone marrow and peripheral blood associated with ongoing differentiation
Authors: de Wolf JT , Muller EW , Hendriks DH , Halie RM , Vellenga E 
Published: October 2019

Abstract
To study the differentiation process of erythroid progenitors from normal human bone marrow and peripheral blood, CD34/CD36 sorted cells were cultured in the presence of Erythropoietin (Epo) and Epo plus mast cell growth factor (MGF). The CD34+/CD36- cell fraction from bone marrow supported 74 +/- 33 erythroid burst forming units (BFU-E)/10(4) cells (mean +/- SD, n = 4) in the presence of Epo, which increased 2.1- fold by coculturing with MGF. However, erythroid colony-forming units (CFU-E) were not cultured from the CD34+/CD36- cell fraction. In contrast, the CD34-/CD36+ cell fraction supported CFU-Es in the presence of Epo (152 +/- 115/10(5)) or Epo plus MGF (180 +/- 112/10(5)), whereas BFU-Es were hardly noticed. However, the transition of the BFu-E to CFU-E was observed by incubating CD34+/CD36- cells (10(4)/100 microL) in suspension with Epo plus MGF for 7 days followed by Epo in the colony assay. This was reflected by the appearance of CD34-/CD36+/Glycophorin A+/CD14- cells. In addition high numbers of CFU- Es (1,000 +/- 150, n = 4) were cultured from this cell fraction. In contrast to bone marrow erythroid progenitors, no peripheral blood CFU- Es were cultured from either the CD36+ or CD36- fraction, whereas BFU- Es were predominantly present in the CD36+ fraction. However, the CD34+ progenitor cell from peripheral blood did have intrinsic capacity to differentiate to CFU-Es because CD34+/CD36- cells incubated with Epo plus MGF for 7 days and followed by Epo in the colony assay, supported high numbers of CFU-Es (1,200 +/- 400, n = 3). To study whether additional growth factors have similar effects on erythroid progenitors, experiments were performed with interleukin 1 (IL-1), IL- 3, and IL-6. IL-1 and IL-6 did not modulate the Epo supported proliferation and differentiation. In contrast, IL-3 in the presence of Epo did support CFU-Es, from CD34+/CD36- cells after 7 days in suspension culture. However, flow cytometry analysis showed that Epo plus IL-3 not only supported CD34-/CD36+/Glycophorin A+ cells but also CD36+/CD14+ cells, indicating the differentiation along different cell lineages. In summary, the data show a phenotypic distinction between bone marrow and peripheral blood erythroid progenitors with regard to CD36 expression. In addition, the results suggest that Epo plus MGF or IL-3 and preincubation in suspension culture are prerequisites for the transition of the BFU-E to the CFU-E.
Lymphocyte predominance Hodgkin's disease: lineage and clonality determination using a single-cell assay
Authors: Delabie J , Tierens A , Wu G , Weisenburger DD , Chan WC 
Published: October 2019

Abstract
Lymphocyte predominance Hodgkin's disease (LPHD) is a clinically indolent condition. Although there is evidence that the putative neoplastic cell in this disease, the “L&H” cell, is of B-cell lineage, there is conflicting data concerning the clonality of these cells. Our study was aimed at clarifying the issue of lineage and clonality of the L&H cells of LPHD using a single-cell assay. Four cases of LPHD were studied. To circumvent the difficulties of obtaining fresh tissue and to be able to study representative cases, a new method was developed to obtain single-cell suspensions of L&H cells from archival formalin- fixed paraffin-embedded tissue. Single L&H cells were identified by morphology and immunostaining for epithelial membrane antigen, isolated using a micropipette, and subjected to polymerase chain reaction (PCR) amplification of the complematarity determining region 3 (CDR3) of the Ig heavy chain (IgH) gene, which is B-cell clone-specific. The PCR products were size-fractionated by polyacrylamide gel electrophoresis and representative products were directly sequenced. Single T cells and small B cells were also isolated from the tissues and used as negative and positive controls, respectively. In all four cases of LPHD, the IgH CDR3 of single L&H cells could be amplified. Within each case, the IgH CDR3 of single L&H cells was found to be of different length or of different sequence. Therefore, our results provide strong evidence for the B-cell origin of the L&H cells and the polyclonal nature of LPHD.