Acute myeloid leukemia requires Hhex to enable PRC2-mediated epigenetic repression of Cdkn2a
Details
Publication Year 2016-01-01, Volume 30, Issue #1, Page 78-91
Journal Title
Genes Dev
Publication Type
Journal Article
Abstract
Unlike clustered HOX genes, the role of nonclustered homeobox gene family members in hematopoiesis and leukemogenesis has not been extensively studied. Here we found 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 expression of the Cdkn2a-encoded tumor suppressors p16(INK4a) and p19(ARF), which are required for growth arrest and myeloid differentiation following Hhex deletion. Mechanistically, we show that Hhex binds to the Cdkn2a locus and directly interacts with the Polycomb-repressive complex 2 (PRC2) to enable H3K27me3-mediated epigenetic repression. Thus, Hhex is a potential therapeutic target that is specifically required for AML stem cells to repress tumor suppressor pathways and enable continued self-renewal.
Publisher
CSH Press
WEHI Research Division(s)
Cancer And Haematology; Bioinformatics
PubMed ID
26728554
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2016-01-29 11:46:10
Last Modified: 2018-01-09 01:00:30
An error has occurred. This application may no longer respond until reloaded. Reload 🗙