Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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

2014-10-31 | E-GEOD-53665 | 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

2014-07-31 | GSE58477 | GEO

Anti-leukemic effect of TGN-1062, a novel CDK7 inhibitor, on AML-leukemic stem cells by targeting RNA modification and Mitochondrial metabolism

Project description:High expression of CDK7, a cell cycle regulator and transcriptional modulator, correlates with poor outcomes in acute myeloid leukemia (AML). We report that TGN-1062, a novel CDK7 inhibitor, exhibits significant antileukemic effects by inhibiting cell growth and inducing apoptosis in AML cell lines and primary CD34+CD38- blasts (enriched for leukemia stem cells; LSCs), while sparing normal CD34+CD38- cells (enriched for hematopoietic stem cells; HSCs). Our study revealed that TGN-1062 treatment in primary CD34+CD38- AML blasts suppress RNA m6A modification by downregulating METTL3/14 proteins, key components of the m6A methyltransferase complex that regulate RNA stability and translation. Decrease in METTL proteins reduced BCL-2 m6A RNA modification and led to increased BCL-2 mRNA decay and protein levels. BCL-2 downregulation resulted in disruption of mitochondrial metabolism and mitofusion in LSCs through decrease of HMGB1/HSPB1 and NRF2/DRP1 signaling, respectively. In vivo, TGN-1062 significantly reduced leukemia burden and prolonged survival in a murine MllPTD/WT/Flt3ITD/ITD AML model and in FLT3-WT and inv(16) AML patient-derived xenografts (PDXs). Increased survival in secondary transplant experiments supported TGN-1062 activity on LSCs. Of note, we proved that TGN-1062 synergized with the BCL-2 inhibitor, venetoclax in eliminating LSCs in both murine and PDX AML models, underscoring its potential as a promising therapeutic approach for AML patients.

2024-11-24 | GSE282364 | 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.

2014-07-31 | E-GEOD-58477 | biostudies-arrayexpress

Transcriptome profiling of quiescent and cytokine induced normal human haematopoietic CD34+ HSPCs, and AML blast cells

Project description:Control group is an essential part of the research design which provide a baseline by elimating variables, bias and other factors that skew the data. Human CD34+ cells are generally used as controls to study myeloid malignancies. This study determines whether fresh or short term cytokine induced CD34+ HSPCs can provide a more appropriate normal control (compared to AML blasts) for target discovery studies. We here determine that the GEP of CD34+ cells that do not undergo ex vivo expansion best match the GEP of minimally differentiated AML blasts and would serve as a better control to identify novel targets in the AML blast population.

2015-12-09 | E-MTAB-3328 | biostudies-arrayexpress

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

Project description:Acute myeloid leukemia (AML) is a heterogeneous group of diseases. Normal cytogenetics (CN) constitutes the single largest group, while trisomy 8 (+8) as a sole abnormality is the most frequent trisomy. How trisomy contributes to tumorigenesis is unknown. We used oligonucleotide-based DNA microarrays to study global gene expression in AML+8 patients with +8 as the sole chromosomal abnormality and AML-CN patients. CD34+ cells purified from normal bone marrow (BM) were also analyzed as a representative heterogeneous population of stem and progenitor cells. Expression patterns of AML patients were clearly distinct from those of CD34+ cells of normal individuals. We show that AML+8 blasts overexpress genes on chromosome 8, estimated at 32% on average, suggesting gene-dosage effects underlying AML+8. Systematic analysis by cellular function indicated up-regulation of genes involved in cell adhesion in both groups of AML compared with CD34+ blasts from normal individuals. Perhaps most interestingly, apoptosis-regulating genes were significantly down-regulated in AML+8 compared with AML-CN. We conclude that the clinical and cytogenetic heterogeneity of AML is due to fundamental biological differences. **NOTE: Migrated from caArray 1.x, identifier='gov.nih.nci.ncicb.caarray:Experiment:1015897559579654:1'

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data