Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A stem cell model identifies two alternative cell fates in CBFA2T3::GLIS2-driven acute megakaryoblastic leukemia initiation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE277004 | GEO | 2025/08/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

A stem cell model identifies two alternative cell fates in CBFA2T3::GLIS2-driven acute megakaryoblastic leukemia initiation (ATAC-seq)

Project description:CBFA2T3::GLIS2 (CG) is an oncogenic fusion protein found in high-risk pediatric acute megakaryoblastic leukemia (AMKL). To gain insight into its leukemogenic mechanism, we developed a disease model based on genetically modified human induced pluripotent stem cells. We found that in this model CG expression disrupts myeloid differentiation via two alternate paths: either by delaying differentiation of aberrant megakaryocytes (aMK) or by locking aberrant megakaryocyte progenitors (aMKP) in a proliferative state akin to AMKL tumor cells. We defined the gene-regulatory networks characterizing both cell states by single-cell transcriptome and epigenome analysis and observed that CG sustains aMKP self-renewal along with cooperators like GATA2 and ERG, while repressing differentiation factors such as SPI1, CEBPA, NFE2, and LYL1. In contrast, in aMKs, CG downregulated drivers of self-renewal and upregulated most but not all lineage-specific differentiation factors. Our findings may contribute to strategies selectively targeting the aMKP state in CG-AMKL patients.

2025-08-15 | GSE276998 | GEO

A stem cell model identifies two alternative cell fates in CBFA2T3::GLIS2-driven acute megakaryoblastic leukemia initiation (ChIP-seq)

2025-08-15 | GSE276996 | GEO

A stem cell model identifies two alternative cell fates in CBFA2T3::GLIS2-driven acute megakaryoblastic leukemia initiation (scRNA-seq)

Project description:CBFA2T3::GLIS2 (CG) is an oncogenic fusion protein found in high-risk pediatric acute megakaryoblastic leukemia (AMKL). To gain insight into its leukemogenic mechanism, we developed a disease model based on genetically modified human induced pluripotent stem cells. We found that CG expression disrupts myeloid differentiation in this model via two alternate paths: either by delaying differentiation of aberrant megakaryocytes (aMK) or by locking aberrant megakaryocyte progenitors (aMKP) in a proliferative state akin to AMKL tumor cells. We characterized the gene-regulatory networks characterizing both cell states by single-cell and epigenome analysis, and observed that CG sustains aMKPs along with cooperators GATA2 and ERG, while repressing differentiation factors like CEBPA, LYL1, and NFE2. In contrast, aMKs maintained many differentiation factors and did not up-regulate regulators of self-renewal. In future, our findings may contribute to improved diagnostic and therapeutic procedures aimed at interconverting cell states in CG-positive patients.

2025-08-15 | GSE277485 | GEO

A stem cell model identifies two alternative cell fates in CBFA2T3::GLIS2-driven acute megakaryoblastic leukemia initiation (RNA-seq)

2025-08-15 | GSE277468 | GEO

A stem cell model identifies two alternative cell fates in CBFA2T3::GLIS2-driven acute megakaryoblastic leukemia initiation (Multiome scRNA-seq/scATAC-seq)

Project description:CBFA2T3::GLIS2 (CG) is an oncogenic fusion protein found in high-risk pediatric acute megakaryoblastic leukemia (AMKL). To gain insight into its leukemogenic mechanism, we developed a disease model based on genetically modified human induced pluripotent stem cells. We found that CG expression disrupts myeloid differentiation in this model via two alternate paths: either by delaying differentiation of aberrant megakaryocytes (aMK) or by locking aberrant megakaryocyte progenitors (aMKP) in a proliferative state akin to AMKL tumor cells. We characterized the gene-regulatory networks characterizing both cell states by single-cell and epigenome analysis, and observed that CG sustains aMKPs along with cooperators GATA2 and ERG, while repressing differentiation factors like CEBPA, LYL1, and NFE2. In contrast, aMKs maintained many differentiation factors and did not up-regulate regulators of self-renewal. In future, our findings may contribute to improved diagnostic and therapeutic procedures aimed at interconverting cell states in CG-positive patients.

2025-08-15 | GSE278751 | GEO

A stem cell model identifies two alternative cell fates in CBFA2T3::GLIS2-driven acute megakaryoblastic leukemia initiation

Project description:A stem cell model identifies two alternative cell fates in CBFA2T3::GLIS2-driven acute megakaryoblastic leukemia initiation

| PRJNA1160199 | ENA

CBFA2T3-GLIS2 model of pediatric acute megakaryoblastic leukemia identifies FOLR1 as a CAR T cell target.

Project description:The CBFA2T3-GLIS2 (C/G) fusion is a product of a cryptic translocation primarily seen in infants and early childhood and is associated with dismal outcome. Here, we demonstrate that the expression of the C/G oncogenic fusion protein promotes the transformation of human cord blood hematopoietic stem and progenitor cells (CB HSPCs) in an endothelial cell coculture system that recapitulates the transcriptome, morphology, and immunophenotype of C/G acute myeloid leukemia (AML) and induces highly aggressive leukemia in xenograft models. Interrogating the transcriptome of C/G-CB cells and primary C/G AML identified a library of C/G-fusion-specific genes that are potential targets for therapy. We developed chimeric antigen receptor (CAR) T cells directed against one of the targets, folate receptor α (FOLR1), and demonstrated their preclinical efficacy against C/G AML using in vitro and xenograft models. FOLR1 is also expressed in renal and pulmonary epithelium, raising concerns for toxicity that must be addressed for the clinical application of this therapy. Our findings underscore the role of the endothelial niche in promoting leukemic transformation of C/G-transduced CB HSPCs. Furthermore, this work has broad implications for studies of leukemogenesis applicable to a variety of oncogenic fusion-driven pediatric leukemias, providing a robust and tractable model system to characterize the molecular mechanisms of leukemogenesis and identify biomarkers for disease diagnosis and targets for therapy.

| S-EPMC9663156 | biostudies-literature

A stem cell model identifies two alternative cell fates in CBFA2T3::GLIS2-driven acute megakaryoblastic leukemia initiation (scRNA-seq)

Project description:A stem cell model identifies two alternative cell fates in CBFA2T3::GLIS2-driven acute megakaryoblastic leukemia initiation (scRNA-seq)

| PRJNA1162503 | ENA

A stem cell model identifies two alternative cell fates in CBFA2T3::GLIS2-driven acute megakaryoblastic leukemia initiation (RNA-seq)

Project description:A stem cell model identifies two alternative cell fates in CBFA2T3::GLIS2-driven acute megakaryoblastic leukemia initiation (RNA-seq)

| PRJNA1162483 | ENA

A stem cell model identifies two alternative cell fates in CBFA2T3::GLIS2-driven acute megakaryoblastic leukemia initiation (ChIP-seq)

Project description:A stem cell model identifies two alternative cell fates in CBFA2T3::GLIS2-driven acute megakaryoblastic leukemia initiation (ChIP-seq)

| PRJNA1160181 | ENA

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