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	Cell of origin in AML: susceptibility to MN1-induced transformation is regulated by the MEIS1/AbdB-like HOX protein complex.
Journal	Formal name：Cancer cell Abbreviation：Cancer Cell ISSN code：18783686/15356108
Domestic / Foregin	Foregin
Volume, Issue, Page	20(1),pp.39-52
Author and coauthor	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
Publication date	2011/07
Summary	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