Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mutated H3 Histones Drive Human Pre-Leukemic Hematopoietic Stem Cell Expansion And Promote Leukemic Aggressiveness

ABSTRACT: Mutated H3 Histones Drive Human Pre-Leukemic Hematopoietic Stem Cell Expansion And Promote Leukemic Aggressiveness

PROVIDER: PRJNA504437 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR8171340.fastq.gz	Fastqsanger.gz
	SRR8171350.fastq.gz	Fastqsanger.gz
	SRR8171360_1.fastq.gz	Fastqsanger.gz
	SRR8171360_2.fastq.gz	Fastqsanger.gz
	SRR8171370_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 56

Similar Datasets

Mutated H3 Histones Drive Human Pre-Leukemic Hematopoietic Stem Cell Expansion And Promote Leukemic Aggressiveness

Project description:Leukemogenesis is a stepwise progression from mutated, pre-neoplastic hematopoietic stem cells (HSCs) to full-blown leukemia. Our ability to prevent or treat de novo and secondary acute myeloid leukemia (AML) is limited by our incomplete understanding of the epigenetic disruption that is central to this process, including improper histone methylation. We performed a comprehensive analysis of 16 histone H3 genes in 434 primary acute myeloid leukemia (AML) samples and identified mutations in adult and pediatric cases (1.6%), with a higher incidence in secondary AML (s-AML) (9%). These included four novel amino acid substitutions (Q69H, A26P, R2Q and R8H) as well as K27M and K27I in H3.1 and H3.3 genes. These mutations are important early events in leukemogenesis as they were observed in pre-leukemic HSCs in two cases and were in the major clones in every sample. Consistent with a role in pre-leukemic HSC clonal expansion, the mutant histones increased functional human HSC frequency and altered differentiation along the erythroid and myeloid lineages, with activity dependent on the specific mutation (K27M, K27I and Q69H). In established human leukemia, the K27M/I mutant histones amplified leukemic aggressiveness, with increased proliferation, expansion of leukemic progenitor and blast cells, and superior competitiveness in vivo. This was associated with increased expression in genes involved in erythrocyte and myeloid differentiation, correlated with a corresponding decrease in histone H3 K27 tri-methylation and increase in K27 acetylation. While histone mutations can co-occur with alterations in RUNX1, we observed that the functional impact of histone mutations is independent of RUNX1 mutations. Taken together, these data establish the involvement of H3 mutations as early drivers of pre-leukemic HSC expansion and leukemogenesis.

2019-04-05 | GSE122273 | GEO

Mutated H3 Histones Drive Human Pre-Leukemic Hematopoietic Stem Cell Expansion And Promote Leukemic Aggressiveness

Project description:Leukemogenesis is a stepwise progression from mutated, pre-neoplastic hematopoietic stem cells (HSCs) to full-blown leukemia. Our ability to prevent or treat acute myeloid leukemia (AML) is limited by our incomplete understanding of the epigenetic disruption that is central to this process, including improper histone methylation. Comprehensive analysis of 16 histone H3 genes in 434 primary AML samples identified Q69H, A26P, R2Q, R8H and K27M/I mutations (1.6%), and a higher incidence in secondary AML (s-AML) (9%). We establish that these mutations are important early events in leukemogenesis. They occur in pre-leukemic HSCs, increase the frequency of functional human HSCs, and alter differentiation. The mutations are present in the major leukemic clones in primary samples, and the mutant histones amplify leukemic aggressiveness with increased proliferation, expansion of leukemic progenitor and blast cells, and superior competitiveness in vivo. These effects are dependent on the specific mutation. Genome-wide analysis of K27 mutants revealed increased expression of genes involved in erythrocyte and myeloid differentiation with a corresponding decrease in histone H3 K27 tri-methylation and increase in K27 acetylation. The functional impact of histone mutations is independent of RUNX1 mutations, although they can co-occur. These data establish the involvement of H3 mutations as initial drivers of pre-cancerous stem cell expansion and leukemogenesis.

| EGAS00001003288 | EGA

Mutant H3 histones drive human pre-leukemic hematopoietic stem cell expansion and promote leukemic aggressiveness.

Project description: Not available

| S-EPMC6599207 | biostudies-literature

Proteomics analysis of ligated and recombinant human histones H3 and H4

Project description:A library of unmodified and differentially modified human histones H3 and H4 was prepared using native chemical ligation as described previously (Bartke et al., 2010; Nakamura et al., 2019). The modification status of histone H3 and H4 products was confirmed by LC-MS/MS.

2023-12-10 | PXD020773 | Pride

mTORC2/Rac1 pathway predisposes cancer aggressiveness in IDH1-mutated glioma

Project description:mTORC2/Rac1 pathway predisposes cancer aggressiveness in IDH1-mutated glioma

| PRJNA613452 | ENA

Mutated H3 Histones Drive Human Pre-Leukemic Hematopoietic Stem Cell Expansion And Promote Leukemic Aggressiveness.

Project description:Data Access Committee EGAC00001001054

| EGAC00001001054 | EGA

PI3K signaling is essential for leukemic transformation of Tet2 mutated pre-leukemic hematopoietic stem cells

Project description:PI3K signaling is essential for leukemic transformation of Tet2 mutated pre-leukemic hematopoietic stem cells

| PRJNA1001939 | ENA

Leukemia aggressiveness is driven by chromatin remodeling and expression changes of core regulators [ChIP-seq]

Project description:Molecular mechanisms driving clonal aggressiveness in leukemia are not fully understood. We tracked and analyzed MLL-rearranged leukemic clones independently evolving towards higher aggressiveness. More aggressive subclones lost their growth differential ex vivo but restored it upon secondary transplantation, suggesting molecular memory of aggressiveness. Development of aggressiveness was associated with clone-specific gradual modulation of chromatin states and expression levels across the genome, with a surprising preferential trend of reversing the earlier changes between normal and leukemic progenitors. To focus on the core aggressiveness program, we identified genes with consistent changes of expression and chromatin marks that were maintained in vivo and ex vivo in both clones. Overexpressing selected core genes (Smad1 as aggressiveness driver, Irx5 and Plag1 as suppressors) affected leukemic progenitor growth in the predicted way and had convergent downstream effects on central transcription factors and repressive epigenetic modifiers, suggesting a broader regulatory network of leukemic aggressiveness.

2026-04-08 | GSE280195 | GEO

Leukemia aggressiveness is driven by chromatin remodeling and expression changes of core regulators [RNA-seq]

2026-04-08 | GSE280194 | GEO

Interactome identification of Histones H3 and H4 in the presence and absence of methyl methanesulfonate (MMS) in the pathogenic yeast Candida glabrata

Project description:The main goal of this project is to identify proteins in Candida glabrata that interact with histones H3 (CgHht) and H4 (CgHhf) under normal and MMS-treatment conditions.

2020-02-21 | PXD016867 | 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