イワサキ マサユキ   Iwasaki Masayuki
  岩崎 正幸
   所属   研究施設 研究施設
   職種   講師
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 The H3K4-Methyl Epigenome Regulates Leukemia Stem Cell Oncogenic Potential.
掲載誌名 正式名:Cancer cell
略  称:Cancer Cell
ISSNコード:18783686/15356108
掲載区分国外
巻・号・頁 28(2),pp.198-209
著者・共著者 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
発行年月 2015/08
概要 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