Dataset Information

SWATH-MS Proteomic Analysis Identifies C/EBPβ Suppression by RUNX1-ETO as a Potential Mediator of Block in Differentiation

ABSTRACT: Acute myeloid leukemia (AML) is a heterogenous disease with multiple morphological, immunophenotypic and genetic features. The t(8;21), which results in the expression of RUNX1-ETO (aka AML1-ETO), is accountable for 12% of AML cases (1). Previously, this fusion protein has been shown to block hematopoietic development of normal human hematopoietic stem and progenitor cells (HSPC), as well as promoting the cells’ self-renewal potential (2,3). Even though several studies have determined the transcriptomic changes observed in cells expressing RUNX1-ETO, there is a paucity of studies quantitating proteomic changes. Given that transcriptional regulation is likely mediated by changes in transcription factor (TF) expression, I hypothesize that RUNX1-ETO leads to TF dysregulation, of which critical components might dictate differentiation blockage.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Bethany Geary

LAB HEAD: Bethany Geary

PROVIDER: PXD046908 | Pride | 2026-07-06

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 58

Similar Datasets

Project description:The t(8;21) translocation fuses the DNA binding domain of the hematopoietic master regulator RUNX1 to the ETO protein. The resultant RUNX1/ETO fusion protein is a leukemia-initiating transcription factor that interferes with RUNX1 function. The result of this interference is a block in differentiation and, finally, the development of acute myeloid leukemia (AML). To obtain insights into RUNX1/ETO-dependant alterations of the epigenetic landscape we measured genome-wide RUNX1- and RUNX1/ETO bound regions in t(8;21) cells and assessed to what extent the effects of RUNX1/ETO on the epigenome depend on its continued expression in established leukemic cells. To this end we determined dynamic alterations of histone acetylation, RNA Polymerase II binding and RUNX1 occupancy in the presence or absence of RUNX1/ETO using a knockdown approach. Combined global assessments of chromatin accessibility and kinetic gene expression data show that RUNX1/ETO controls the expression of important regulators of hematopoietic differentiation and self-renewal. We show that selective removal of RUNX1/ETO leads to a widespread reversal of epigenetic reprogramming and a genome-wide re-distribution of RUNX1 binding, resulting in the inhibition of leukemic proliferation and self-renewal and the induction of differentiation. This demonstrates that RUNX1/ETO represents a pivotal therapeutic target in AML. This SuperSeries is composed of the following subset Series: GSE29222: Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding [ChIP-Seq and DNAse-Hypersensitivity data] GSE29223: Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding [expression array data] GSE34540: Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding (ChIP-seq) GSE34594: Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding (Illumina expression) Refer to individual Series

			Action	DRS
	RDRUN01_10_1.wiff	Wiff
	RDRUN01_10_1.wiff.scan	Wiff
	RDRUN01_10_2.wiff	Wiff
	RDRUN01_10_2.wiff.scan	Wiff
	RDRUN01_11_1.wiff	Wiff

Dataset Information

SWATH-MS Proteomic Analysis Identifies C/EBPβ Suppression by RUNX1-ETO as a Potential Mediator of Block in Differentiation

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets