Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genes regulated in EML1 cells expressing the TEL-AML1 oncogene after 5 and 7 days of treatment with IL7 and FLT3 ligand.

ABSTRACT: The t(12;21) translocation is the most common genetic rearrangement in childhood acute lymphoblastic leukemia (ALL) and gives rise to the TEL-AML1 fusion gene, which functions as a transcription factor. TEL-AML1 expression in EML1 cells results in an impairment of differentiation along the B-lymphoid lineage. We analyzed gene expression profiles of EML1 cells after expression of TEL-AML1

ORGANISM(S): Mus musculus

SUBMITTER: Myriam Alcalay

PROVIDER: E-GEOD-64919 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The TEL-AML1 fusion protein of acute lymphoblastic leukemia modulates IRF3 activity during early B-cell differentiation.

de Laurentiis A A Hiscott J J Alcalay M M

Oncogene 20150420 49

The t(12;21) translocation is the most common genetic rearrangement in childhood acute lymphoblastic leukemia (ALL) and gives rise to the TEL-AML1 fusion gene. Many studies on TEL-AML1 describe specific properties of the fusion protein, but a thorough understanding of its function is lacking. We exploited a pluripotent hematopoietic stem/progenitor cell line, EML1, and generated a cell line (EML-TA) stably expressing the TEL-AML1 fusion protein. EML1 cells differentiate to mature B-cells followi ...[more]

PMID: 25893288

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Project description: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. Keywords: Acute lymphoblastic leukemia, gene expression profiles, TEL/AML1 fusion transcript, functional annotation

Project description: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 â??RUNX1, TCFL5, TNFRSF7, CBFA2T3, CD9, SCARB1, TP53INP1, ACVR1C, PIK3C3, EGFL7, SEMA6A, CTGF, LSP1, TFPIâ?? 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. Experiment Overall Design: We carried out a prospective multicentric study on childhood B-ALL leukemia to elucidate the molecular processes involved in TEL/AML1-positive leukemia. All the patients included in this study received treatment according to the French FRALLE 2000 trial. We used Agilent whole-genome oligo-chips (44K-G4112A) to compare the gene expression signatures of TEL/AML1-positive patients to those of TEL/AML1-negative patients with no recurrent chimeric products irrespective of their clinical risk category. Previous microarray gene expression studies had revealed the effect of chromosomal alteration on transcription profiles, so we excluded from our cohort those patients with other recurrent chromosomal translocations or fusion transcripts (BCR/ABL, E2A/PBX1, MLL rearrangements). We then searched for the biological pathways associated with genes differentially expressed in TEL/AML1-positive leukemia (ETV6/RUNX1).

Dataset Information

Genes regulated in EML1 cells expressing the TEL-AML1 oncogene after 5 and 7 days of treatment with IL7 and FLT3 ligand.

Publications

The TEL-AML1 fusion protein of acute lymphoblastic leukemia modulates IRF3 activity during early B-cell differentiation.

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