Acute myeloid leukemia requires Hhex to enable PRC2-mediated epigenetic repression of Cdkn2a (RNA-Seq)
Transcriptomics Dataset
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General Information
AccessionGSE74018
TitleAcute myeloid leukemia requires Hhex to enable PRC2-mediated epigenetic repression of Cdkn2a (RNA-Seq)
DescriptionUnlike clustered HOX genes, the role of non-clustered homeobox gene family members in hematopoiesis and leukemogenesis has not been extensively studied. Here we find that the Hematopoietically-expressed Homeobox gene, Hhex, is overexpressed in acute myeloid leukemia (AML) and is essential for the initiation and propagation of MLL-ENL induced AML, but dispensable for normal myelopoiesis, indicating a specific requirement for Hhex for leukemic growth. Loss of Hhex leads to upregulated expression of the tumor suppressors p16INK4a and p19ARF, which are required for growth arrest and myeloid differentiation following Hhex deletion. Mechanistically, we show that Hhex binds to the Cdkn2a locus and is required for H3K27Me3-mediated repression of this locus. Thus, Hhex is a novel therapeutic target that is specifically required for AML stem cells to repress tumor suppressor pathways and enable continued self-renewal.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE74018
RepositoryGene Expression Omnibus
Tools used to analyze the dataset
Dataset Accession
ARCHS4
Published September 2017
ARCHS4 provides access to gene counts from HiSeq 2000 and HiSeq 2500 platforms for human and mouse experiments from GEO ...
4645
Clustergrammer
Published October 2017
Web-based tool for visualizing and analyzing high-dimensional data as interactive and shareable heatmaps
4645
Canned Analyses generated with the dataset
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Interactive heatmap visualization of RNA-seq dataset GSE74018
ARCHS4, Clustergrammer
Highly interactive web-based heatmap visualization of the top 500 most variable genes in t...
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