2. Academic Validation
  3. EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation

EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation

  • Cancer Cell. 2013 May 13;23(5):677-92. doi: 10.1016/j.ccr.2013.04.011.
Wendy Béguelin 1,  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
Affiliations

Affiliation

  • 1 Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY 10021, USA.
PMID: 23680150 DOI: 10.1016/j.ccr.2013.04.011
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.

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