EZH2 Is Required for Germinal Center Formation and Somatic EZH2 Mutations Promote Lymphoid Transformation Academic Article uri icon

Overview

MeSH Major

  • B-Lymphocytes
  • Cell Transformation, Neoplastic
  • Germinal Center
  • Mutation
  • Polycomb Repressive Complex 2

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.

authors

publication date

  • May 13, 2013

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3681809

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2013.04.011

PubMed ID

  • 23680150

Additional Document Info

start page

  • 677

end page

  • 92

volume

  • 23

number

  • 5