| Literature DB >> 26190263 |
Stephen H K Wong1, David L Goode2, Masayuki Iwasaki1, Michael C Wei1, Hsu-Ping Kuo1, Li Zhu1, Dominik Schneidawind3, Jesus Duque-Afonso1, Ziming Weng4, Michael L Cleary5.
Abstract
The genetic programs that maintain leukemia stem cell (LSC) self-renewal and oncogenic potential have been well defined; however, the comprehensive epigenetic landscape that sustains LSC cellular identity and functionality is less well established. We report that LSCs in MLL-associated leukemia reside in an epigenetic state of relative genome-wide high-level H3K4me3 and low-level H3K79me2. LSC differentiation is associated with reversal of these broad epigenetic profiles, with concomitant downregulation of crucial MLL target genes and the LSC maintenance transcriptional program that is driven by the loss of H3K4me3, but not H3K79me2. The H3K4-specific demethylase KDM5B negatively regulates leukemogenesis in murine and human MLL-rearranged AML cells, demonstrating a crucial role for the H3K4 global methylome in determining LSC fate.Entities:
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Year: 2015 PMID： 26190263 PMCID： PMC4536132 DOI： 10.1016/j.ccell.2015.06.003
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743