| Literature DB >> 23680150 |
Wendy Béguelin1, Relja Popovic, Matt Teater, Yanwen Jiang, Karen L Bunting, Monica Rosen, Hao Shen, Shao Ning Yang, Ling Wang, Teresa Ezponda, Eva Martinez-Garcia, Haikuo Zhang, Yupeng Zheng, Sharad K Verma, Michael T McCabe, Heidi M Ott, Glenn S Van Aller, Ryan G Kruger, Yan Liu, Charles F McHugh, David W Scott, Young Rock Chung, Neil Kelleher, Rita Shaknovich, Caretha L Creasy, Randy D Gascoyne, Kwok-Kin Wong, Leandro Cerchietti, Ross L Levine, Omar Abdel-Wahab, Jonathan D Licht, Olivier Elemento, Ari M Melnick.
Abstract
The EZH2 histone methyltransferase is highly expressed in germinal center (GC) B cells and targeted by somatic mutations in B cell lymphomas. Here, we find that EZH2 deletion or pharmacologic inhibition suppresses GC formation and functions. EZH2 represses proliferation checkpoint genes and helps establish bivalent chromatin domains at key regulatory loci to transiently suppress GC B cell differentiation. Somatic mutations reinforce these physiological effects through enhanced silencing of EZH2 targets. Conditional expression of mutant EZH2 in mice induces GC hyperplasia and accelerated lymphomagenesis in cooperation with BCL2. GC B cell (GCB)-type diffuse large B cell lymphomas (DLBCLs) are mostly addicted to EZH2 but not the more differentiated activated B cell (ABC)-type DLBCLs, thus clarifying the therapeutic scope of EZH2 targeting.Entities:
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Year: 2013 PMID： 23680150 PMCID： PMC3681809 DOI： 10.1016/j.ccr.2013.04.011
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743