induces NF-κB signaling-driven peripheral T cell lymphoma.

Title induces NF-κB signaling-driven peripheral T cell lymphoma.
Publication TypeJournal Article
Year of Publication2021
AuthorsMoon 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
JournalNat Cancer
Date Published2021 Jan

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.

Alternate JournalNat Cancer
PubMed ID33928261
PubMed Central IDPMC8081346
Grant ListP01 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.

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