Implementation of Innovative Techniques in Routine Diagnosis of Childhood Acute Leukemia: Analysis of Genome and Transcriptome by Micro-array
Condition: Acute Leukemia
MeSH terms: Leukemia; Acute Disease
Study type: Interventional

Summary: 
      Acute leukemias are a heterogeneous group of malignancies characterized by the abnormal
      proliferation of a cell clone in the bone marrow, having as origin lymphocytic or myeloid
      lineage. The repertoire of mutations that determine the leukemic transformation, complex and
      variable depending on the tumor type and progression of the disease, combined in the same
      cell of balanced and unbalanced chromosomal aberrations, point mutations and epigenetic
      abnormalities.

      The project presented here is part of a comprehensive approach to diagnosis of hematologic
      malignancies of children. Using comparative genomic hybridization on microarray (or array-
      CGH) and transcriptome analysis by microarray, two innovative techniques for a comprehensive
      analysis of the genome and transcriptome , offer new perspectives identifying molecular
      defects . These techniques provide new elements in the identification of acute leukemia at
      diagnosis may identify new prognostic factors to optimize the care of patients.

      This project involves both the Department of Medical Genetics (Prof. N. LEVY ) regarding the
      identification of genomic abnormalities associated with childhood leukemia , the Laboratory
      of Hematology of the Hospital de la Timone ( Prof. Pierre Morange ) in terms of the
      phenotypic characterization of tumor cells, and the Onco - Hematology Pediatric Department
      (Prof. Michel Gerard ) which provides diagnosis, treatment , monitoring and the bone marrow
      of children with hematologic malignancies . The following project is mainly focused on the
      identification of genomic abnormalities (deletions and duplications) and abnormalities in
      gene expression to identify a genetic profile ensuring a better classification within the
      different groups risk .

      The project we propose is centered on the identification of genomic abnormalities , changing
      the number of copies of certain regions of the genome or determining loss of heterozygosity ,
      and the identification of changes in the level of gene expression by using two analytical
      techniques, comparative genomic hybridization on microarray (or array- CGH) and expression
      studies with microarrays . The data generated will , for the identification of " molecular
      signatures " , the classification of patients according to prognosis , variations in
      treatment response and survival.

      The originality of this project lies in the use of these new tools in the diagnosis of
      hematological malignancies in children. This pilot study will be conducted with commercial
      Affymetrix , will develop the chips ' processing' , dedicated , enriched probes corresponding
      to genes involved in leukemogenesis , with high discriminatory power in identifying these
      signatures.

      The data published in the specialized literature from the study of large series of patients
      show that microarrays provide important information for the diagnosis and therapeutic
      management of patients. It is for this reason that in the end we hope to integrate these
      analyzes in routine diagnosis to complement other analyzes ( phenotyping , identification of
      fusion genes and sequencing) in order to further characterize the abnormal cells leukemia and
      establish an " identity card of leukemia .
    


Intervention name(s): blood draw
Intervention type(s): Genetic
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic