2. Academic Validation
  3. 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

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

  • Oncoimmunology. 2022 Oct 11;11(1):2134536. doi: 10.1080/2162402X.2022.2134536.
Fenglian Que 1,  Lihong Zhang 2 3,  Taoli Wang 4,  Meifang Xu 5,  Wangen Li 1,  Shengbing Zang 2 3
Affiliations

Affiliations

  • 1 Department of Endocrinology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510260, China.
  • 2 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, China.
  • 3 Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, China.
  • 4 Department of Pathology, Zhuzhou Central Hospital, Zhuzhou, Hunan, 412007, China.
  • 5 Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.
PMID: 36249275 DOI: 10.1080/2162402X.2022.2134536
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 with AITL. Our findings suggest that PON2 associated with RHOA G17V mutation might control the direction of the molecular agents-based AITL and provide a new therapeutic target in AITL.

Keywords

AITL; NF-κB pathway; PON2; RHOA; mutation.

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