Title | induces NF-κB signaling-driven peripheral T cell lymphoma. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Moon CS, Reglero C, Cortes JR, S Quinn A, Alvarez S, Zhao J, Lin W-HW, Cooke AJ, Abate F, Soderquist CR, Fiñana C, Inghirami G, Campo E, Bhagat G, Rabadan R, Palomero T, Ferrando AA |
Journal | Nat Cancer |
Volume | 2 |
Issue | 1 |
Pagination | 98-113 |
Date Published | 2021 Jan |
ISSN | 2662-1347 |
Abstract | Angioimmunoblastic T cell lymphoma (AITL) and peripheral T cell lymphoma not-otherwise-specified (PTCL, NOS) have poor prognosis and lack driver actionable targets for directed therapies in most cases. Here we identify as a recurrent oncogenic gene fusion in AITL and PTCL, NOS tumors. Mechanistically, we show that FYN-TRAF3IP2 leads to aberrant NF-κB signaling downstream of T cell receptor activation. Consistent with a driver oncogenic role, FYN-TRAF3IP2 expression in hematopoietic progenitors induces NF-κB-driven T cell transformation in mice and cooperates with loss of the tumor suppressor in PTCL development. Moreover, abrogation of NF-κB signaling in -induced tumors with IκB kinase inhibitors delivers strong anti-lymphoma effects and . These results demonstrate an oncogenic and pharmacologically targetable role for FYN-TRAF3IP2 in PTCLs and call for the clinical testing of anti-NF-κB targeted therapies in these diseases. |
DOI | 10.1038/s43018-020-00161-w |
Alternate Journal | Nat Cancer |
PubMed ID | 33928261 |
PubMed Central ID | PMC8081346 |
Grant List | P01 CA229100 / CA / NCI NIH HHS / United States P30 CA013696 / CA / NCI NIH HHS / United States R01 CA216981 / CA / NCI NIH HHS / United States R35 CA210065 / CA / NCI NIH HHS / United States |
Related Faculty:
Giorgio Inghirami, M.D.