| Literature DB >> 21156283 |
Lixin Rui1, N C Tolga Emre, Michael J Kruhlak, Hye-Jung Chung, Christian Steidl, Graham Slack, George W Wright, Georg Lenz, Vu N Ngo, Arthur L Shaffer, Weihong Xu, Hong Zhao, Yandan Yang, Laurence Lamy, R Eric Davis, Wenming Xiao, John Powell, David Maloney, Craig J Thomas, Peter Möller, Andreas Rosenwald, German Ott, Hans Konrad Muller-Hermelink, Kerry Savage, Joseph M Connors, Lisa M Rimsza, Elias Campo, Elaine S Jaffe, Jan Delabie, Erlend B Smeland, Dennis D Weisenburger, Wing C Chan, Randy D Gascoyne, David Levens, Louis M Staudt.
Abstract
Chromosome band 9p24 is frequently amplified in primary mediastinal B cell lymphoma (PMBL) and Hodgkin lymphoma (HL). To identify oncogenes in this amplicon, we screened an RNA interference library targeting amplicon genes and thereby identified JAK2 and the histone demethylase JMJD2C as essential genes in these lymphomas. Inhibition of JAK2 and JMJD2C cooperated in killing these lymphomas by decreasing tyrosine 41 phosphorylation and increasing lysine 9 trimethylation of histone H3, promoting heterochromatin formation. MYC, a major target of JAK2-mediated histone phosphorylation, was silenced after JAK2 and JMJD2C inhibition, with a corresponding increase in repressive chromatin. Hence, JAK2 and JMJD2C cooperatively remodel the PMBL and HL epigenome, offering a mechanistic rationale for the development of JAK2 and JMJD2C inhibitors in these diseases.Entities:
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Year: 2010 PMID： 21156283 PMCID： PMC3049192 DOI： 10.1016/j.ccr.2010.11.013
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743