Mouse model of RHOA G17V mutation in Peripheral T-Cell Lymphoma. Mus musculus

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive lymphoid tumor derived from malignant transformation of T follicular helper (Tfh) cells. Genetically, AITL is characterized by loss of function mutations in the Ten-Eleven Translocation 2 (TET2) epigenetic tumor suppressor and a highly recurrent mutation (p.Gly17Val, G17V) in the RHOA small GTPase gene Moreover, RHOA G17V expression in Tet2 deficient hematopoietic progenitors resulted in the specific development of lymphoid tumors resembling human AITL. Notably, inhibition of ICOS signaling impaired the growth of RHOA G17V-induced mouse lymphomas in vivo, thus providing a potential new rational approach for the treatment of AITL. Overall design: We analyzed mRNA expression profiles of primary tumor cells expressing Rhoa G17V or Rhoa wild type.

血管免疫母细胞性T细胞淋巴瘤（Angioimmunoblastic T-cell lymphoma, AITL）是一类起源于T滤泡辅助（T follicular helper, Tfh）细胞恶性转化的侵袭性淋巴肿瘤。遗传学层面，AITL的特征性分子改变包括十-十一易位2（Ten-Eleven Translocation 2, TET2）表观遗传抑癌基因的功能缺失突变，以及RHOA小GTP酶基因中高频复现的p.Gly17Val突变（简称G17V）。此外，在Tet2缺陷的造血祖细胞中表达RHOA G17V，可特异性诱导出形态与表型类似人类AITL的淋巴肿瘤。值得注意的是，体内阻断诱导性T细胞共刺激分子（ICOS）信号通路可显著抑制RHOA G17V诱导的小鼠淋巴瘤生长，由此为AITL的临床治疗提供了潜在的全新合理策略。整体实验设计：本研究分析了分别表达Rhoa G17V突变体与野生型Rhoa的原代肿瘤细胞的mRNA表达谱。