IWASAKI Masayuki
   Department   Research Institutes and Facilities, Research Institutes and Facilities
   Position   Assistant Professor
Article types Original article
Language English
Peer review Peer reviewed
Title The H3K4-Methyl Epigenome Regulates Leukemia Stem Cell Oncogenic Potential.
Journal Formal name:Cancer cell
Abbreviation:Cancer Cell
ISSN code:18783686/15356108
Domestic / ForeginForegin
Volume, Issue, Page 28(2),pp.198-209
Author and coauthor Wong Stephen H K, Goode David L, Iwasaki Masayuki, Wei Michael C, Kuo Hsu-Ping, Zhu Li, Schneidawind Dominik, Duque-Afonso Jesus, Weng Ziming, Cleary Michael L
Publication date 2015/08
Summary 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.
DOI 10.1016/j.ccell.2015.06.003
PMID 26190263