| Literature DB >> 32396861 |
Wendy Béguelin1, Matt Teater2, Cem Meydan3, Kenneth B Hoehn4, Jude M Phillip5, Alexey A Soshnev6, Leandro Venturutti5, Martín A Rivas5, María T Calvo-Fernández5, Johana Gutierrez5, Jeannie M Camarillo7, Katsuyoshi Takata8, Karin Tarte9, Neil L Kelleher7, Christian Steidl8, Christopher E Mason10, Olivier Elemento11, C David Allis6, Steven H Kleinstein12, Ari M Melnick13.
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.Entities:
Keywords: EZH2; epigenetic dysregulation; follicular lymphoma; germinal center; immune microenvironment
Mesh：
Substances：
Year: 2020 PMID： 32396861 PMCID： PMC7298875 DOI： 10.1016/j.ccell.2020.04.004
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743