Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression profiling of imatinib-treated and untreated human Hematopoetic progenitors expressing the ETV6-PDGFRB oncogene

ABSTRACT: In order to investigate the mechanism whereby TEL-PDGF-beta (ETV6-PDGFRB) interferes with human hematopoietic progenitors proliferation and differentiation, we analyzed the gene expression response downstream this oncogene. CD34+ cells infected with lentivirus coding for TEL-PDGFRb were cultured for 7 days in the absence of cytokines. Using Affymetrix microarrays, we compared gene expression in these cells and in cells treated for 4 h with low dose imatinib (Glivec), a potent PDGFR inhibitor, to switch off TEL-PDGFRb signaling. This experiment was performed in three biological replicates. In each replicate gene expression profiling from CD34+ HSCs expressing TEL-PDGFRb untreated with Glivec was compared to the corresoniding treated condition. Total RNA were extracted from transduced CD34+ cells using Trizol reagent (Invitrogen) and the RNeasy kit (QIAGEN).

ORGANISM(S): Homo sapiens

SUBMITTER: Jean-Baptiste Demoulin

PROVIDER: E-GEOD-28698 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

ETV6-PDGFRB and FIP1L1-PDGFRA stimulate human hematopoietic progenitor cell proliferation and differentiation into eosinophils: the role of nuclear factor-κB.

Montano-Almendras Carmen P CP Essaghir Ahmed A Schoemans Hélène H Varis Inci I Noël Laura A LA Velghe Amélie I AI Latinne Dominique D Knoops Laurent L Demoulin Jean-Baptiste JB

Haematologica 20120122 7

<h4>Background</h4>ETV6-PDGFRB (also called TEL-PDGFRB) and FIP1L1-PDGFRA are receptor-tyrosine kinase fusion genes that cause chronic myeloid malignancies associated with hypereosinophilia. The aim of this work was to gain insight into the mechanisms whereby fusion genes affect human hematopoietic cells and in particular the eosinophil lineage.<h4>Design and methods</h4>We introduced ETV6-PDGFRB and FIP1L1-PDGFRA into human CD34(+) hematopoietic progenitor and stem cells isolated from umbilical ...[more]

PMID: 22271894

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Project description: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:<br> <br> "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."<br> <br> 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. <br> <br> 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.

Dataset Information

Gene expression profiling of imatinib-treated and untreated human Hematopoetic progenitors expressing the ETV6-PDGFRB oncogene

Publications

ETV6-PDGFRB and FIP1L1-PDGFRA stimulate human hematopoietic progenitor cell proliferation and differentiation into eosinophils: the role of nuclear factor-κB.

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