| First Author | Moon CS | Year | 2021 |
| Journal | Nat Cancer | Volume | 2 |
| Issue | 1 | Pages | 98-113 |
| PubMed ID | 33928261 | Mgi Jnum | J:310389 |
| Mgi Id | MGI:6755619 | Doi | 10.1038/s43018-020-00161-w |
| Citation | Moon CS, et al. (2021) FYN-TRAF3IP2 induces NF-kappaB signaling-driven peripheral T cell lymphoma. Nat Cancer 2(1):98-113 |
| abstractText | 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 FYN-TRAF3IP2 as a recurrent oncogenic gene fusion in AITL and PTCL, NOS tumors. Mechanistically, we show that FYN-TRAF3IP2 leads to aberrant NF-kappaB signaling downstream of T cell receptor activation. Consistent with a driver oncogenic role, FYN-TRAF3IP2 expression in hematopoietic progenitors induces NF-kappaB-driven T cell transformation in mice and cooperates with loss of the Tet2 tumor suppressor in PTCL development. Moreover, abrogation of NF-kappaB signaling in FYN-TRAF3IP2-induced tumors with IkappaB kinase inhibitors delivers strong anti-lymphoma effects in vitro and in vivo. These results demonstrate an oncogenic and pharmacologically targetable role for FYN-TRAF3IP2 in PTCLs and call for the clinical testing of anti-NF-kappaB targeted therapies in these diseases. |
