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 Cell of origin in AML: susceptibility to MN1-induced transformation is regulated by the MEIS1/AbdB-like HOX protein complex.
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 20(1),pp.39-52
著者・共著者 Heuser Michael, Yun Haiyang, Berg Tobias, Yung Eric, Argiropoulos Bob, Kuchenbauer Florian, Park Gyeongsin, Hamwi Iyas, Palmqvist Lars, Lai Courteney K, Leung Malina, Lin Grace, Chaturvedi Anuhar, Thakur Basant Kumar, Iwasaki Masayuki, Bilenky Mikhail, Thiessen Nina, Robertson Gordon, Hirst Martin, Kent David, Wilson Nicola K, Göttgens Bertie, Eaves Connie, Cleary Michael L, Marra Marco, Ganser Arnold, Humphries R Keith
発行年月 2011/07
概要 Pathways defining susceptibility of normal cells to oncogenic transformation may be valuable therapeutic targets. We characterized the cell of origin and its critical pathways in MN1-induced leukemias. Common myeloid (CMP) but not granulocyte-macrophage progenitors (GMP) could be transformed by MN1. Complementation studies of CMP-signature genes in GMPs demonstrated that MN1-leukemogenicity required the MEIS1/AbdB-like HOX-protein complex. ChIP-sequencing identified common target genes of MN1 and MEIS1 and demonstrated identical binding sites for a large proportion of their chromatin targets. Transcriptional repression of MEIS1 targets in established MN1 leukemias demonstrated antileukemic activity. As MN1 relies on but cannot activate expression of MEIS1/AbdB-like HOX proteins, transcriptional activity of these genes determines cellular susceptibility to MN1-induced transformation and may represent a promising therapeutic target.
DOI 10.1016/j.ccr.2011.06.020
PMID 21741595