title: Five distinct biological processes and 14 differentially expressed genes characterize TEL/AML1-positive leukemia.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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. virginie.gandemer@chu-rennes.fr
authors.forename: Virginie
authors.initials: V
authors.lastname: Gandemer
authors.forename: Anne-Gaëlle
authors.initials: AG
authors.lastname: Rio
authors.forename: Marie
authors.initials: M
authors.lastname: de Tayrac
authors.forename: Vonnick
authors.initials: V
authors.lastname: Sibut
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Mottier
authors.forename: Béatrice
authors.initials: B
authors.lastname: Ly Sunnaram
authors.forename: Catherine
authors.initials: C
authors.lastname: Henry
authors.forename: Annabelle
authors.initials: A
authors.lastname: Monnier
authors.forename: Christian
authors.initials: C
authors.lastname: Berthou
authors.forename: Edouard
authors.initials: E
authors.lastname: Le Gall
authors.forename: André
authors.initials: A
authors.lastname: Le Treut
authors.forename: Claudine
authors.initials: C
authors.lastname: Schmitt
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Le Gall
authors.forename: Jean
authors.initials: J
authors.lastname: Mosser
authors.forename: Marie-Dominique
authors.initials: MD
authors.lastname: Galibert
mesh_terms: D002648:Child; D002881:Chromosomes, Human, Pair 12; D002891:Chromosomes, Human, Pair 21; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007223:Infant; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic / Q000235:genetics; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein