| First Author | Cortes JR | Year | 2018 |
| Journal | Cancer Cell | Volume | 33 |
| Issue | 2 | Pages | 259-273.e7 |
| PubMed ID | 29398449 | Mgi Jnum | J:257764 |
| Mgi Id | MGI:6119201 | Doi | 10.1016/j.ccell.2018.01.001 |
| Citation | Cortes JR, et al. (2018) RHOA G17V Induces T Follicular Helper Cell Specification and Promotes Lymphomagenesis. Cancer Cell 33(2):259-273.e7 |
| abstractText | Angioimmunoblastic T cell lymphoma (AITL) is an aggressive tumor derived from malignant transformation of T follicular helper (Tfh) cells. AITL is characterized by loss-of-function mutations in Ten-Eleven Translocation 2 (TET2) epigenetic tumor suppressor and a highly recurrent mutation (p.Gly17Val) in the RHOA small GTPase. Yet, the specific role of RHOA G17V in AITL remains unknown. Expression of Rhoa G17V in CD4(+) T cells induces Tfh cell specification; increased proliferation associated with inducible co-stimulator (ICOS) upregulation and increased phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase signaling. Moreover, RHOA G17V expression together with Tet2 loss resulted in development of AITL in mice. Importantly, Tet2(-/-)RHOA G17V tumor proliferation in vivo can be inhibited by ICOS/PI3K-specific blockade, supporting a driving role for ICOS signaling in Tfh cell transformation. |
