モチヅキ　マキコ   Mochidzuki Makiko   望月　牧子    所属   医学部 医学科    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Ezh2 loss promotes development of myelodysplastic syndrome but attenuates its predisposition to leukaemic transformation.
掲載誌名	正式名：Nature communications 略　 称：Nat Commun ISSNコード：20411723/20411723
掲載区分	国外
巻・号・頁	5,pp.4177
著者・共著者	Sashida Goro, Harada Hironori, Matsui Hirotaka, Oshima Motohiko, Yui Makiko, Harada Yuka, Tanaka Satomi, Mochizuki-Kashio Makiko, Wang Changshan, Saraya Atsunori, Muto Tomoya, Hayashi Yoshihiro, Suzuki Kotaro, Nakajima Hiroshi, Inaba Toshiya, Koseki Haruhiko, Huang Gang, Kitamura Toshio, Iwama Atsushi
発行年月	2014/06
概要	Loss-of-function mutations of EZH2, a catalytic component of polycomb repressive complex 2 (PRC2), are observed in ~\n10% of patients with myelodysplastic syndrome (MDS), but are rare in acute myeloid leukaemia (AML). Recent studies have shown that EZH2 mutations are often associated with RUNX1 mutations in MDS patients, although its pathological function remains to be addressed. Here we establish an MDS mouse model by transducing a RUNX1S291fs mutant into hematopoietic stem cells and subsequently deleting Ezh2. Ezh2 loss significantly promotes RUNX1S291fs-induced MDS. Despite their compromised proliferative capacity of RUNX1S291fs/Ezh2-null MDS cells, MDS bone marrow impairs normal hematopoietic cells via selectively activating inflammatory cytokine responses, thereby allowing propagation of MDS clones. In contrast, loss of Ezh2 prevents the transformation of AML via PRC1-mediated repression of Hoxa9. These findings provide a comprehensive picture of how Ezh2 loss collaborates with RUNX1 mutants in the pathogenesis of MDS in both cell autonomous and non-autonomous manners.
DOI	10.1038/ncomms5177
PMID	24953053