| First Author | Béguelin W | Year | 2020 |
| Journal | Cancer Cell | Volume | 37 |
| Issue | 5 | Pages | 655-673.e11 |
| PubMed ID | 32396861 | Mgi Jnum | J:289028 |
| Mgi Id | MGI:6416666 | Doi | 10.1016/j.ccell.2020.04.004 |
| Citation | Beguelin W, et al. (2020) Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response. Cancer Cell 37(5):655-673.e11 |
| abstractText | 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. |
