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Activity of a stem cell enhancer influences stem cell programs and clinical outcome in leukaemia

ABSTRACT: Chip-chip data from primary human AML patient blasts, normal CD34+ HSCs, normal neutrophils and normal T cells with H3K9 and H3K27 antibodies. Gene expression profiling from primary human AML patient blasts and CD34+ normal cells. Analysis of the chromatin landscape of the ERG locus using H3K9 and H3K27 as markers of euchromatin and heterochromatin respectively. Analysis of ERG expression in AML patients with normal CD34+ HSCs as control.

ORGANISM(S): Homo sapiens

PROVIDER: GSE38865 | GEO | 2013/04/04

SECONDARY ACCESSION(S): PRJNA169080

REPOSITORIES: GEO

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Activity of a stem cell enhancer influences stem cell programs and clinical outcome in leukaemia

Project description:Chip-chip data from primary human AML patient blasts, normal CD34+ HSCs, normal neutrophils and normal T cells with H3K9 and H3K27 antibodies. Gene expression profiling from primary human AML patient blasts and CD34+ normal cells. Analysis of the chromatin landscape of the ERG locus using H3K9 and H3K27 as markers of euchromatin and heterochromatin respectively. Analysis of ERG expression in AML patients with normal CD34+ HSCs as control. Correlation of the activity of a stem cell enhancer at the ERG locus in AML primary patient blasts with their transcriptome and clinical outcome data.

2013-04-04 | E-GEOD-38865 | biostudies-arrayexpress

High ERG expression in human HSPCs promotes progenitor but not stem cell proliferation and molecular signatures that are enriched in high ERG leukemia.

Project description:ERG is an Ets-transcription factor required for normal blood stem cell development. High ERG expression in acute myeloid leukemia (AML) and acute T-cell lymphoblastic leukemia (T-ALL) is associated with a stem cell signature and poor prognosis. In murine over-expression models, human ERG is a potent oncogene that induces both T-ALL and AML. However the functional and molecular consequences of high ERG expression in normal hematopoietic stem/progenitors (HSPCs), and how this contributes to leukemia development, are unknown. Here we show that retroviral transduction of ERG into human CD34+ cells and maintenance of ERG at levels present in high ERG AML results in altered myeloid and T cell differentiation and an increase in the self-renewal capacity of transduced progenitors but not the more primitive stem cell compartment. Integrated analysis of genome-wide expression in high ERG CD34+ and ERG binding profiles in HSPCs revealed that these functional characteristics were accompanied by an expression signature that was enriched in normal HSCs, high ERG AMLs, early T-cell precursor (ETP)-ALLs and leukemic stem cell signatures associated with poor clinical outcome. The proliferative advantage of high ERG progenitors may provide a cellular context for the acquisition and propagation of mutations that contribute to the pathogenesis of leukaemia. RNA sequencing in ERG overexpressing human CD34+ cells

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Differential methylation in CN-AML preferentially targets non-CGI regions and is dictated by DNMT3A mutational status and associated with predominant hypomethylation of HOX genes

2014-07-31 | GSE58477 | GEO

Integrated nuclear proteomics and transcriptomics identifies new high frequency dysregulated targets in acute myeloid leukemia

Project description:Acute myeloid leukemia (AML) is characterized by developmental arrest which is thought to arise from transcriptional dysregulation of myeloid development programs. Here, we have analyzed the transcriptome of AML blasts in comparison with normal human CD34+ cells using the HTA 2.0 gene chip. We have compared 18 minimally differentiated AML blasts with cord blood derived normal human CD34+ cells - this study is performed as a parallel analysis to compliment the nuclear proteomic studies.

2019-10-02 | E-MTAB-3873 | biostudies-arrayexpress

Differential methylation in CN-AML preferentially targets non-CGI regions and is dictated by DNMT3A mutational status and associated with predominant hypomethylation of HOX genes

Project description:The study investigated the abberrent DNA methylation in correlation with gene expression in cytogenetic normal acute myeloid leukemia. CN-AML blasts isolated from patient bone marrow aspriation were compared to CD34+ cell population from healthy donors by DNA methylation array and affymetrix gene expression microarray. Bisulfited genomic DNA from patients and normal materials were hybirdized to Illumia Infinium Human Methylation 450K Beadchip. Gene expression profiling on selected patient cohort are publish aviable.

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caArray_krahe-00060: Expression profiling reveals fundamental biological differences in acute myeloid leukemia

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2015-06-26 | GSE70284 | GEO

caArray_krahe-00060: Expression profiling reveals fundamental biological differences in acute myeloid leukemia

2015-06-26 | E-GEOD-70284 | biostudies-arrayexpress

Gene expression analysis in primary blasts of AML patients and CD34+normal progenitors after 6 hours of HDACi treatment.

Project description:AML blasts and CD34+ normal progenitors were treated with SAHA, and gene expression profiles were compared to 6-hours treatments. The analysis revealed commonly regulated genes in these systems by HDACi.

2017-03-01 | GSE54873 | GEO

Transcription profiling of human hematopoietic cells from 38 healthy donors and leukemic blasts from 26 AML patients

Project description:Acute myeloid leukemia (AML) is one of the most common and deadly forms of hematopoietic malignancies. We hypothesized that microarray studies could identify previously unrecognized expression changes that only occur only in AML blasts. We were particularly interested in those genes with increased expression in AML, believing that these genes may be potential therapeutic targets. Experiment Overall Design: We compared gene expression profiles between normal hematopoietic cells from 38 healthy donors and leukemic blasts from 26 AML patients. Normal hematopoietic samples included CD34+ selected cells (N = 18), unselected bone marrows (N = 10), and unselected peripheral bloods (N = 10).

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