|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|
|Date Published||2021 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 Journal||Nat Cancer|
|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
Giorgio Inghirami, M.D.