| Literature DB >> 21741597 |
Kathrin M Bernt1, Nan Zhu, Amit U Sinha, Sridhar Vempati, Joerg Faber, Andrei V Krivtsov, Zhaohui Feng, Natalie Punt, Amanda Daigle, Lars Bullinger, Roy M Pollock, Victoria M Richon, Andrew L Kung, Scott A Armstrong.
Abstract
The histone 3 lysine 79 (H3K79) methyltransferase Dot1l has been implicated in the development of leukemias bearing translocations of the Mixed Lineage Leukemia (MLL) gene. We identified the MLL-fusion targets in an MLL-AF9 leukemia model, and conducted epigenetic profiling for H3K79me2, H3K4me3, H3K27me3, and H3K36me3 in hematopoietic progenitor and leukemia stem cells (LSCs). We found abnormal profiles only for H3K79me2 on MLL-AF9 fusion target loci in LSCs. Inactivation of Dot1l led to downregulation of direct MLL-AF9 targets and an MLL translocation-associated gene expression signature, whereas global gene expression remained largely unaffected. Suppression of MLL translocation-associated gene expression corresponded with dependence of MLL-AF9 leukemia on Dot1l in vivo. These data point to DOT1L as a potential therapeutic target in MLL-rearranged leukemia.Entities:
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Year: 2011 PMID： 21741597 PMCID： PMC3329803 DOI： 10.1016/j.ccr.2011.06.010
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743