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ABSTRACT: The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells

PROVIDER: PRJNA153305 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR444504.fastq.gz	Fastqsanger.gz
	SRR444505.fastq.gz	Fastqsanger.gz
	SRR444506.fastq.gz	Fastqsanger.gz
	SRR444507.fastq.gz	Fastqsanger.gz
	SRR444508.fastq.gz	Fastqsanger.gz

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Similar Datasets

The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells

Project description:This SuperSeries is composed of the following subset Series: GSE36346: The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells (ChIP-Seq data) GSE36347: The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells (expression data) Refer to individual Series

2012-03-28 | E-GEOD-36348 | biostudies-arrayexpress

The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells (ChIP-Seq data)

Project description:Using a mouse model of human MLL-AF9 leukemia, we identified the lysine-specific demethylase KDM1A (LSD1 or AOF2) as an essential regulator of leukemia stem cell (LSC) potential. KDM1A acts at genomic loci bound by MLL-AF9 to sustain expression of the associated oncogenic program, thus preventing differentiation and apoptosis. In vitro and in vivo pharmacologic targeting of KDM1A using tranylcypromine analogues active in the nanomolar range phenocopied Kdm1a knockdown in both murine and primary human AML cells exhibiting MLL translocations. By contrast, the clonogenic and repopulating potential of normal hematopoietic stem and progenitor cells was spared. Our data establish KDM1A as a key effector of the differentiation block in MLL leukemia which may be selectively targeted to therapeutic effect. To investigate the effects of Kdm1a KD on histone modifications, we performed chromatin immunoprecipitation followed by next-generation sequencing (ChIP-Seq) in control and Kdm1a KD MLL-AF9 AML cells for dimethyl-H3K4 and dimethyl-H3K9, as well as for trimethyl-H3K4 and trimethyl-H3K9. Dimethyl-H3K4 and dimethyl-H3K9 are targeted for demethylation by KDM1A. For each of these histone modifications, we compared the mean ChIP-Seq signal across and around protein coding genes bound by the MLL-AF9 oncoprotein (Bernt et al., 2011) with the mean signal from genes not bound by MLL-AF9 expressed at high, middle or low levels.

2012-03-28 | E-GEOD-36346 | biostudies-arrayexpress

Mus musculus

Project description:The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells (expression data)

| PRJNA155567 | ENA

The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells (ChIP-Seq data)

2012-03-29 | GSE36346 | GEO

The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells (expression data)

Project description:Using a mouse model of human MLL-AF9 leukemia, we identified the lysine-specific demethylase KDM1A (LSD1 or AOF2) as an essential regulator of leukemia stem cell (LSC) potential. KDM1A acts at genomic loci bound by MLL-AF9 to sustain expression of the associated oncogenic program, thus preventing differentiation and apoptosis. In vitro and in vivo pharmacologic targeting of KDM1A using tranylcypromine analogues active in the nanomolar range phenocopied Kdm1a knockdown in both murine and primary human AML cells exhibiting MLL translocations. By contrast, the clonogenic and repopulating potential of normal hematopoietic stem and progenitor cells was spared. Our data establish KDM1A as a key effector of the differentiation block in MLL leukemia which may be selectively targeted to therapeutic effect. To investigate the genetic program regulated by KDM1A in murine MLL-AF9 AML cells enriched for LSCs, we compared the transcriptome of KIT+Gr1+ control and Kdm1a KD cells using exon arrays soon after initiation of KD. At this time, there was no immunophenotypic evidence of differentiation in Kdm1a KD cells. Exonic expression values were condensed into gene-level expression summaries, which represent the mean expression value of the probe sets targeting the length of a given protein coding gene. Three separate samples from two different animals were used. Kdm1a KD samples were compared with control samples. Total six arrays.

2012-03-28 | E-GEOD-36347 | biostudies-arrayexpress

Mus musculus

Project description:The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells (ChIP-Seq data)

| PRJNA155565 | ENA

The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells (expression data)

Project description:Using a mouse model of human MLL-AF9 leukemia, we identified the lysine-specific demethylase KDM1A (LSD1 or AOF2) as an essential regulator of leukemia stem cell (LSC) potential. KDM1A acts at genomic loci bound by MLL-AF9 to sustain expression of the associated oncogenic program, thus preventing differentiation and apoptosis. In vitro and in vivo pharmacologic targeting of KDM1A using tranylcypromine analogues active in the nanomolar range phenocopied Kdm1a knockdown in both murine and primary human AML cells exhibiting MLL translocations. By contrast, the clonogenic and repopulating potential of normal hematopoietic stem and progenitor cells was spared. Our data establish KDM1A as a key effector of the differentiation block in MLL leukemia which may be selectively targeted to therapeutic effect. To investigate the genetic program regulated by KDM1A in murine MLL-AF9 AML cells enriched for LSCs, we compared the transcriptome of KIT+Gr1+ control and Kdm1a KD cells using exon arrays soon after initiation of KD. At this time, there was no immunophenotypic evidence of differentiation in Kdm1a KD cells. Exonic expression values were condensed into gene-level expression summaries, which represent the mean expression value of the probe sets targeting the length of a given protein coding gene.

2012-03-29 | GSE36347 | GEO

The H3K4-methyl epigenome regulates MLL leukemia stem cell oncogenic potential

Project description:The genetic programs that maintain leukemia stem cell (LSC) self-renewal and oncogenic potential have been well defined, however the epigenetic landscape that determines their cellular identity and functionality has not been established. We report that LSCs in MLL-associated leukemia are maintained in an epigenetic state defined by relative genome-wide high-level H3K4me3 methylation and low level H3K79me2. LSC differentiation is associated with dynamic reversal of these broad epigenetic profiles and concomitant down-regulation of the LSC maintenance transcriptional program. LSCs also share with embryonic stem cells a large subset of genes with bivalent histone marks related to embryonic development. The histone demethylase KDM5B negatively regulates MLL-induced leukemogenesis demonstrating the crucial role of the H3K4 global methylome for determining leukemia stem cell fate. Investigation of multiple histone modification marks and RNA Pol II in ckit+ and ckit- cells isolated and fractionated from MLL leukemia mice.

2015-06-26 | E-GEOD-60193 | biostudies-arrayexpress

Histone demethylase KDM4A-mediated promotion of PAF1/NFATC2 expression is required for oncogenesis in MLL-AF9 acute myeloid leukemia [RNA-seq]

Project description:In this study we identified the histone demethylase KDM4A as an essential and selective regulator of AML oncogenic potential. RNAseq was used to follow the changes in gene expression following KDM4A knockdown in MLL-AF9 human AML THP-1 cells

2021-01-17 | GSE125374 | GEO

Histone demethylase KDM4A-mediated promotion of PAF1/NFATC2 expression is required for oncogenesis in MLL-AF9 acute myeloid leukemia [ChIP-seq]

Project description:In this study we identified the histone demethylase KDM4A as an essential and selective regulator of AML oncogenic potential. ChIPseq was used to identify KDM4A bound genes and follow changes in H3K9me2/3 and H3K27me3 following KDM4A knockdown in MLL-AF9 human AML THP-1 cells

2021-01-17 | GSE125375 | GEO

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