Angioimmunoblastic T-cell lymphoma-like lymphadenopathy in mice transgenic for human RHOA with p.Gly17Val mutation

OncoImmunology

卷:9

Jaesang Kim¹  Yukyung Jun¹  Daekee Lee¹  Gyu Jin Lee¹  Sanghyuk Lee¹  Yoon Kyung Jeon²  Hae Yong Yoo³ 

[1] Ewha Womans University;

[2] Seoul National University College of Medicine;

[3] Sungkyunkwan University;

关键词: angioimmunoblastic t-cell lymphoma;    rhoa;    follicular helper t-cell;    pd-1;   

DOI  :  10.1080/2162402X.2020.1746553

来源: DOAJ

【 摘 要 】

A missense mutation in RHOA encoding p.Gly17 Val has been reported to occur frequently in angioimmunoblastic T-cell lymphoma (AITL). Here, we describe a murine model which expresses the human RHOA mutant gene product in a T-cell specific manner and develops AITL-like symptoms. Most transgenic mice feature with latency one or two enlarged lymph nodes characterized by aberrant lymph node architecture, extensive lymphocytic infiltration, extrafollicular meshwork of follicular dendritic cells (FDC) and arborized endothelial venules. Importantly, we provide evidence for expansion of PD-1+ follicular helper T (Tfh) cells which are the neoplastic cells of AITL. In addition, we saw proliferation of B-cells leading to hypergammaglobulinemia and the presence of dominant T cell clonal populations. Transplantation of lymph node cells to immunocompromised mice partly recreated lymphadenopathy after a long latency and with low penetrance suggesting that cells have undergone partial transformation to a premalignant state. Transcriptomic profiling revealed that the gene expression pattern within affected lymph nodes of the mice closely resembles that of AITL patients with the identical RHOA p.Gly17 Val mutation. The murine model should, therefore, be useful in dissecting pathogenesis of AITL at the molecular level particularly for the cases with the RHOA p.Gly17Val mutation.

【 授权许可】

Unknown