RHOA G17V induces T follicular helper cell specification and involves angioimmunoblastic T-cell lymphoma via upregulating the expression of PON2 through an NF-κB-dependent mechanism.

ABSTRACT: Angioimmunoblastic T-cell lymphoma (AITL) is a malignant hematologic tumor arising from T follicular helper (Tfh) cells. High-throughput genomic sequencing studies have shown that AITL is characterized by a novel highly recurring somatic mutation in RHOA, encoding p.Gly17Val (RHOA G17V). However, the specific role of RHOA G17V in AITL remains unknown. Here, we demonstrated that expression of Rhoa G17V in CD4⁺ T cells increased cell proliferation and induces Tfh cell specification associated with Pon2 upregulation through an NF-κB-dependent mechanism. Further, loss of Pon2 attenuated oncogenic function induced by genetic lesions in Rhoa. In addition, an abnormality of RHOA G17V mutation and PON2 expression is also detected in patients wit

SUBMITTER: Que F 

PROVIDER: S-EPMC9559328 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature