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 / ForeginForegin
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