Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response. Academic Article uri icon

Overview

abstract

  • Follicular lymphomas (FLs) are slow-growing, indolent tumors containing extensive follicular dendritic cell (FDC) networks and recurrent EZH2 gain-of-function mutations. Paradoxically, FLs originate from highly proliferative germinal center (GC) B cells with proliferation strictly dependent on interactions with T follicular helper cells. Herein, we show that EZH2 mutations initiate FL by attenuating GC B cell requirement for T cell help and driving slow expansion of GC centrocytes that become enmeshed with and dependent on FDCs. By impairing T cell help, mutant EZH2 prevents induction of proliferative MYC programs. Thus, EZH2 mutation fosters malignant transformation by epigenetically reprograming B cells to form an aberrant immunological niche that reflects characteristic features of human FLs, explaining how indolent tumors arise from GC B cells.

publication date

  • May 11, 2020

Research

keywords

  • B-Lymphocytes
  • Cell Transformation, Neoplastic
  • Cellular Reprogramming
  • Enhancer of Zeste Homolog 2 Protein
  • Lymphoma, B-Cell
  • Lymphoma, Follicular
  • Mutation

Identity

PubMed Central ID

  • PMC7298875

Scopus Document Identifier

  • 85084238011

Digital Object Identifier (DOI)

  • 10.1016/j.ccell.2020.04.004

PubMed ID

  • 32396861

Additional Document Info

volume

  • 37

issue

  • 5