Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [ChIP-Seq]

ABSTRACT: Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [ChIP-Seq]

PROVIDER: PRJNA1062377 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [ChIP-Seq]

Project description:Germline, mono-allelic mutations in RUNX1 cause familial platelet disorder (RUNX1-FPD) that evolves into myeloid malignancy (FPD-MM): MDS or AML. FPD-MM commonly harbors co-mutations in the second RUNX1 allele and/or other epigenetic regulators. Here we utilized patient-derived (PD) FPD-MM cells and established the first FPD-MM AML cell line (GMR-AML1). GMR-AML1 cells exhibited active super-enhancers of MYB, MYC, BCL2 and CDK6, augmented expressions of c-Myc, c-Myb, EVI1 and PLK1 and surface markers of AML stem cells. In longitudinally studied bone marrow cells from a patient at FPD-MM vs RUNX1-FPD state, we confirmed increased chromatin accessibility and mRNA expressions of MYB, MECOM and BCL2 in FPD-MM cells. GMR-AML1 and PD FPD-MM cells were sensitive to homoharringtonine (HHT or omacetaxine) or mebendazole-induced lethality, associated with repression of c-Myc, EVI1, PLK1, CDK6 and MCL1. Co-treatment with MB and the PLK1 inhibitor volasertib exerted synergistic in vitro lethality in GMR-AML1 cells. In luciferase-expressing GMR-AML1 xenograft model, MB, omacetaxine or volasertib monotherapy, or co-treatment with MB and volasertib, significantly reduced AML burden and improved survival in the immune-depleted mice. These findings highlight the molecular features of FPD-MM progression and demonstrate HHT, MB and/or volasertib as effective agents against cellular models of FPD-MM.

2024-02-01 | GSE252739 | GEO

Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [scRNA-Seq]

2024-02-01 | GSE252745 | GEO

Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [ATAC-Seq]

2024-02-01 | GSE252743 | GEO

Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [Stranded mRNA-Seq]

2024-02-01 | GSE252740 | GEO

Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM).

Project description:Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM).

| PRJNA1062371 | ENA

Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [scRNA-Seq]

Project description:Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [scRNA-Seq]

| PRJNA1062378 | ENA

Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [ATAC-Seq]

Project description:Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [ATAC-Seq]

| PRJNA1062379 | ENA

Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [Stranded mRNA-Seq]

Project description:Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [Stranded mRNA-Seq]

| PRJNA1062376 | ENA

Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM).

| S-EPMC10844204 | biostudies-literature

Transcription profiling of human CD34+ cells from familial platelet disorder

Project description:Characterize the genes deregulated in CD34 positive cells from peripheral blood of FPD/AML patients harbouring two different RUNX1 mutations. RUNX1 (also called AML1), a DNA-binding subunit of the CBF transcription factor family, is a master regulatory gene in hematopoiesis and acts as a tumour suppressor. Heterozygous germ line alterations in RUNX1 lead to a familial platelet disorder with a propensity to develop acute myeloid leukemia (FPD/AML). Although RUNX1 abnormalities per se are not sufficient to induce full-blown leukemia in FPD, this pathology represents a valuable model to understand how RUNX1 germ line mutations predispose to acquisition of additional genetic changes leading to leukemia transformation. To investigate how RUNX1 may predispose to leukemia, we performed a comparative study between two pedigrees harbouring different RUNX1 mutations, one associated with only thrombocytopenia (R139stop) and the other leading to thrombocytopenia and leukemic predisposition (R174Q).

2010-09-11 | E-TABM-792 | biostudies-arrayexpress

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