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

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, Rennes cedex, France.
BMC Genomics (Impact Factor: 3.99). 02/2007; 8(1):385. DOI: 10.1186/1471-2164-8-385
Source: PubMed


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.
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.
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.

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    • "To the best of our knowledge, only one other group has previously analyzed the expression patterns of primary E/R-positive ALL cases and assigned them to GO categories [11]. Consistent with our data, they also observed a distinct association with the categories “cell differentiation”, “cell proliferation”, “apoptosis”, “cell motility” and “response to wounding”. "
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    • "TNFAIP6 also identified by [11] was involved in intracellular signaling (integral to plasma membrane, receptor activity, signal transducer activity, cell surface receptor-linked signal transduction, cell motility, G-protein-coupled receptor protein signaling pathway, cell–cell signaling, development, and organogenesis, morphogenesis and extracellular region). TCFL5 is one of the nine selected genes reported by [48] as being the most biologically relevant and being able to independently differentiate between TEL/AML1 positive and TEL/AML1 negative patients. The lymphoid specific gene, MME that is highly expressed in ALL samples and under expressed in MLL samples has a function in early B-cell development [34]. "
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