Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Disrupting mitochondrial copper distribution inhibits leukemic stem cell self-renewal

ABSTRACT: Disrupting mitochondrial copper distribution inhibits leukemic stem cell self-renewal

PROVIDER: PRJNA609914 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR11218100_1.fastq.gz	Fastqsanger.gz
	SRR11218100_2.fastq.gz	Fastqsanger.gz
	SRR11218101_1.fastq.gz	Fastqsanger.gz
	SRR11218101_2.fastq.gz	Fastqsanger.gz
	SRR11218102_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 112

Similar Datasets

Disrupting mitochondrial copper distribution inhibits leukemic stem cell self-renewal

Project description:Leukemic stem cells (LSC) rely on oxidative metabolism and are differentially sensitive to targeting mitochondrial pathways, which spares normal hematopoietic cells. A subset of mitochondrial proteins are folded in the intermembrane space via the mitochondrial intermembrane assembly (MIA) pathway. We found increased mRNA expression of MIA pathway substrates in acute myeloid leukemia (AML) stem cells. Therefore, we evaluated the effects of inhibiting this pathway in AML. Genetic and chemical inhibition of ALR reduces AML growth and viability, disrupts LSC self-renewal and induces their differentiation. ALR inhibition preferentially decreases its substrate COX17, a mitochondrial copper chaperone and knockdown of COX17 phenocopies ALR loss. Inhibiting ALR and COX17 increases mitochondrial copper levels which in turn inhibit S-Adenosylhomocysteine Hydrolase (SAHH) and lower levels of S-adenosylmethionine (SAM), DNA methylation, and chromatin accessibility to lower LSC viability. These results provide insight into mechanisms through which mitochondrial copper controls epigenetic status and viability of LSCs.

2020-04-14 | GSE146252 | GEO

PHF6 suppresses self-renewal of leukemic stem cells in AML

Project description:PHF6 suppresses self-renewal of leukemic stem cells in AML

| PRJNA1128120 | ENA

A STAT5B-CD9 axis determines self-renewal in hematopoietic and leukemic stem cells

Project description:The transcription factors STAT5A and STAT5B are critical in hematopoiesis and leukemia. They are widely believed to have redundant functions but we describe a unique role for STAT5B in driving the self-renewal of hematopoietic and leukemic stem cells (HSCs/LSCs). We find STAT5B to be specifically activated in HSCs and LSCs, where it induces many genes associated with quiescence and self-renewal, including the surface marker CD9. Levels of CD9 represent a prognostic marker for patients with STAT5-driven leukemia and our findings suggest that anti-CD9 antibodies may be useful in their treatment to target and eliminate LSCs. We show that it is vital to consider STAT5A and STAT5B as distinct entities in normal and malignant hematopoiesis.

2021-12-31 | GSE178648 | GEO

IKZF2 is required for myeloid leukemic stem cells by driving self-renewal and inhibiting the myeloid differentiation program I

Project description:We report that IKZF2 is required for maintaining chromatin accessibility in leukemic stem cells in myeloid leukemia. RNA seq and ATAC-seq were performed to investigate the changes in chromatin accessibility of differentially expressed genes in leukemic stem cells when IKZF2 was absent. We found that IKZF2 maintains open accessibility in self-renewal transcription factor motifs such as HOXA9 sites whereas motifs of differentiation transcription factors including C/EBPs are kept closed.

2017-12-21 | GSE108367 | GEO

IKZF2 is required for myeloid leukemic stem cells by driving self-renewal and inhibiting the myeloid differentiation program II

2018-09-29 | GSE120623 | GEO

Kdm6b is Required for Self-Renewal of Normal and Leukemic Stem Cells Under Proliferative Stress

Project description:Recent studies have indicated that the histone 3 lysine 27 (H3K27me2/3) demethylase KDM6B (JMJD3) is frequently upregulated in a myriad of blood disorders including myelodysplastic syndrome (MDS), T-cell acute lymphoblastic leukemia (T-ALL), and multiple myeloma (MM) suggesting it may have important functions in the pathogenesis of hematopoietic cancers. Here, we sought to determine the role of Kdm6b in hematopoietic stem cell (HSC) fate decisions under normal and malignant conditions to evaluate its potential as a therapeutic target. We show that loss of Kdm6b leads to a significant reduction in phenotypic and functional HSCs in adult mice, and that Kdm6b is necessary for HSC self-renewal in response to inflammatory, genotoxic and oncogenic stress. Additionally, we show that loss of Kdm6b in HSCs leads to a stress-response gene expression signature in native HSCs that is independent of its demethylase activity. Loss of Kdm6b lead to increased expression of a subset of genes implicated in HSC quiescence (e.g. Fos, Jun, Ier2, Dusp1, Zfp36). Upon inflammatory or replicative stress, HSCs deficient for Kdm6b are not able to efficiently resolve this gene expression program, leading to increased quiescence and a self-renewal block, forcing them to differentiate. These findings show that Kdm6b is necessary for self-renewal of normal and leukemic stem cells, and suggest inhibiting Kdm6b in blood cancers in the presence of proliferative agents may force differentiation and eventual depletion of leukemic stem cells.

2019-07-17 | GSE110378 | GEO

PLCG1 is required for AML1-ETO leukemia stem cell self-renewal

Project description:In an effort to identify novel drugs targeting fusion-oncogene induced acute myeloid leukemia (AML), we performed high-resolution proteomic analysis. In AML1-ETO (AE) driven AML we uncovered a deregulation of phospholipase C (PLC) signaling. We identified PLCgamma 1 (PLCG1) as a specific target of the AE fusion protein which is induced after AE binding to intergenic regulatory DNA elements. Genetic inactivation of PLCG1 in murine and human AML inhibited AML1-ETO dependent self-renewal programs, leukemic proliferation, and leukemia maintenance in vivo. In contrast, PLCG1 was dispensable for normal hematopoietic stem- and progenitor cell function. These findings are extended to and confirmed by pharmacologic perturbation of Ca++-signaling in AML1-ETO AML cells, indicating that the PLCG1 pathway poses an important therapeutic target for AML1-ETO positive leukemic stem cells.

2021-11-04 | PXD026374 | Pride

MLL-Menin inhibition reverses pre-leukemic progenitor self-renewal induced by NPM1c mutations

Project description:MLL-Menin inhibition reverses pre-leukemic progenitor self-renewal induced by NPM1c mutations

| PRJNA532379 | ENA

A STAT5B-CD9 axis determines self-renewal in hematopoietic and leukemic stem cells

Project description:A STAT5B-CD9 axis determines self-renewal in hematopoietic and leukemic stem cells

| PRJNA739891 | ENA

AML1-ETO induced leukemia stem cell self-renewal depends on Plcg1

Project description:High-resolution proteomic analysis of acute myeloid leukemia (AML) stem cells identified phospholipase C- and Ca++-signaling pathways to be differentially regulated in AML1-ETO (AE) driven leukemia. Phospholipase C gamma 1 (Plcg1) could be identified as a direct target of the AE fusion. Genetic Plcg1 inactivation abrogated disease initiation by AE, reduced intracellular Ca++-release and inhibited AE-driven self-renewal programs. In AE-induced leukemia, Plcg1 deletion significantly reduced disease penetrance, number of leukemia stem cells and abrogated leukemia development in secondary recipient hosts. In human AE-positive leukemic cells inactivation of Plcg1 reduced colony formation and AML development in vivo. In contrast, Plcg1 was dispensable for maintenance of murine and human hematopoietic stem- and progenitor cells (HSPCs). Pharmacologic inhibition of Ca++-signaling downstream of Plcg1 resulted in impaired proliferation and self-renewal capacity in AE-driven AML. Thus, the Plcg1 pathway represents a novel specific vulnerability of AE-driven leukemia and poses an important new therapeutic target.

2022-01-12 | PXD011251 | Pride

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