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

Title
Angioimmunoblastic T-cell lymphoma-like lymphadenopathy in mice transgenic for human RHOA with p.Gly17Val mutation
Authors
Lee, Gyu JinJun, YukyungYoo, Hae YongJeon, Yoon KyungLee, DaekeeLee, SanghyukKim, Jaesang
Ewha Authors
이상혁김재상이대기
SCOPUS Author ID
이상혁scopusscopus; 김재상scopus; 이대기scopus
Issue Date
2020
Journal Title
ONCOIMMUNOLOGY
ISSN
2162-402XJCR Link
Citation
ONCOIMMUNOLOGY vol. 9, no. 1
Keywords
Angioimmunoblastic T-celllymphomaRHOAfollicular helper T-cellPD-1
Publisher
TAYLOR &

FRANCIS INC
Indexed
SCIE; SCOPUS WOS
Document Type
Article
Abstract
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.
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DOI
10.1080/2162402X.2020.1746553
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자연과학대학 > 생명과학전공 > Journal papers
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