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Open Access Highly Accessed Research article

Five distinct biological processes and 14 differentially expressed genes characterize TEL/AML1-positive leukemia

Virginie Gandemer13, Anne-Gaëlle Rio1, Marie de Tayrac2, Vonnick Sibut1, Stéphanie Mottier1, Béatrice Ly Sunnaram4, Catherine Henry5, Annabelle Monnier6, Christian Berthou7, Edouard Le Gall3, André Le Treut12, Claudine Schmitt8, Jean-Yves Le Gall1, Jean Mosser126 and Marie-Dominique Galibert12*

Author Affiliations

1 CNRS UMR 6061 Laboratoire de Génétique et Développement, Equipe Régulation transcriptionnelle et oncogenèse, Université de Rennes-1, Faculté de Médecine, IFR140 GFAS, 2 av du Pr Léon Bernard, CS 34317, 35043 Rennes cedex, France

2 Department of Biochemistry and Molecular Genetics, Medical Genomic Unit, CHU Rennes, France

3 Department of OncoPediatrics, CHU Rennes, France

4 Laboratory of Hematology Rennes, France

5 Laboratory of Cytogenetics, CHU Rennes, France

6 Ouest-Genopole ®, transcriptomic platform, IFR 140, Rennes, France

7 Laboratory of Hematology, CHU Brest, France

8 Department of OncoPediatrics, CHU Nancy, France

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BMC Genomics 2007, 8:385  doi:10.1186/1471-2164-8-385

Published: 23 October 2007

Abstract

Background

The t(12;21)(p13;q22) translocation is found in 20 to 25% of cases of childhood B-lineage acute lymphoblastic leukemia (B-ALL). This rearrangement results in the fusion of ETV6 (TEL) and RUNX1 (AML1) genes and defines a relatively uniform category, although only some patients suffer very late relapse. TEL/AML1-positive patients are thus an interesting subgroup to study, and such studies should elucidate the biological processes underlying TEL/AML1 pathogenesis. We report an analysis of gene expression in 60 children with B-lineage ALL using Agilent whole genome oligo-chips (44K-G4112A) and/or real time RT-PCR.

Results

We compared the leukemia cell gene expression profiles of 16 TEL/AML1-positive ALL patients to those of 44 TEL/AML1-negative patients, whose blast cells did not contain any additional recurrent translocation. Microarray analyses of 26 samples allowed the identification of genes differentially expressed between the TEL/AML1-positive and negative ALL groups. Gene enrichment analysis defined five enriched GO categories: cell differentiation, cell proliferation, apoptosis, cell motility and response to wounding, associated with 14 genes -RUNX1, TCFL5, TNFRSF7, CBFA2T3, CD9, SCARB1, TP53INP1, ACVR1C, PIK3C3, EGFL7, SEMA6A, CTGF, LSP1, TFPI – highlighting the biology of the TEL/AML1 sub-group. These results were first confirmed by the analysis of an additional microarray data-set (7 patient samples) and second by real-time RT-PCR quantification and clustering using an independent set (27 patient samples). Over-expression of RUNX1 (AML1) was further investigated and in one third of the patients correlated with cytogenetic findings.

Conclusion

Gene expression analyses of leukemia cells from 60 children with TEL/AML1-positive and -negative B-lineage ALL led to the identification of five biological processes, associated with 14 validated genes characterizing and highlighting the biology of the TEL/AML1-positive ALL sub-group.