Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human hematopoietic stem cells, pro-B cells and TEL-AML1 tranduced cord blood cells to study TEL-AML1 associated childhood leukemia

ABSTRACT: The microarray data presented here relate to a study on TEL-AML1 associated childhood leukemia (Hong et al, 2008) the abstract of which is as follows:

"Understanding cancer pathogenesis requires knowledge of not only the specific contributory genetic mutations but also the cellular framework in which they arise and function. Here we explore the clonal evolution of childhood precursor B-cell acute lymphoblastic leukemia characterised by a chromosomal translocation generating a TEL-AML1 fusion gene. We identify a cell compartment in leukemic children which can propagate leukemia when transplanted in mice. By studying a monochorionic twin pair, one pre-leukemic and one with frank leukemia, we establish the lineal relationship between these "tumor-propagating" cells and the pre-leukemic cell in which the TEL-AML1 fusion first arises or has functional impact. Analysis of TEL-AML1 transduced cord blood cells suggests that TEL-AML1 functions as a first-hit mutation by endowing this pre-leukemic cell with altered self-renewal and survival properties."

The cells used to generate the microarray data were obtained as follows: We prospectively isolated CD34+CD38-/lowCD19+ cells from NOD/SCID mice transplanted with TEL-AML1-transduced human cord blood cells and compared their gene expression profiles, ascertained by affymetrix microarray analysis (see methods), to control 'hematopoietic stem cells' (HSCs immunophenotypically-defined as CD34+CD38-/lowCD19-) and pro-B cells (immunophenotypically-defined as CD34+CD38+CD19+) isolated from NOD/SCID animals transplanted with control vector transduced cord blood cells.

While these different populations were obtained from three independent transduction and transplantation experiments, the data were generated from small numbers of cells and have not been validated by independent analyses such as RQ-PCR or protein analysis. They should therefore be regarded as preliminary in nature and we would therefore caution against detailed analysis of individual gene expression profiles based on these particular datasets. This caveat aside, the data may provide a broad overview of gene expression profiles in these cell types and such analyses suggest that TEL-AML1 generates a novel population of cells that contain features of both stem cells and committed B progenitors (Hong et al 2008). We are currently repeating the analyses using larger numbers of cells and more replicates together with appropriate cell populations from ALL patients and will post these data online when they become available.

ORGANISM(S): Homo sapiens

SUBMITTER: Shamit Soneji

PROVIDER: E-MEXP-1403 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Initiating and cancer-propagating cells in TEL-AML1-associated childhood leukemia.

Hong Dengli D Gupta Rajeev R Ancliff Philip P Atzberger Ann A Brown John J Soneji Shamit S Green Joanne J Colman Sue S Piacibello Wanda W Buckle Veronica V Tsuzuki Shinobu S Greaves Mel M Enver Tariq T

Science (New York, N.Y.) 20080101 5861

Understanding cancer pathogenesis requires knowledge of not only the specific contributory genetic mutations but also the cellular framework in which they arise and function. Here we explore the clonal evolution of a form of childhood precursor-B cell acute lymphoblastic leukemia that is characterized by a chromosomal translocation generating a TEL-AML1 fusion gene. We identify a cell compartment in leukemic children that can propagate leukemia when transplanted in mice. By studying a monochorio ...[more]

PMID: 18202291

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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

Transcription profiling of human hematopoietic stem cells, pro-B cells and TEL-AML1 tranduced cord blood cells to study TEL-AML1 associated childhood leukemia

Publications

Initiating and cancer-propagating cells in TEL-AML1-associated childhood leukemia.

Similar Datasets

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