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The H3K4-Methyl Epigenome Regulates Leukemia Stem Cell Oncogenic Potential.
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.
Afiliação
  • Wong SH; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Goode DL; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, VIC 3010, Australia.
  • Iwasaki M; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Wei MC; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Kuo HP; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Zhu L; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Schneidawind D; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Duque-Afonso J; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Weng Z; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Cleary ML; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: mcleary@stanford.edu.
Cancer Cell ; 28(2): 198-209, 2015 Aug 10.
Article em En | MEDLINE | ID: mdl-26190263
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Neoplásicas / Histonas / Leucemia / Transformação Celular Neoplásica / Epigênese Genética Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Neoplásicas / Histonas / Leucemia / Transformação Celular Neoplásica / Epigênese Genética Idioma: En Ano de publicação: 2015 Tipo de documento: Article