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

Gyu Jin Lee, Yukyung Jun, Hae Yong Yoo, Yoon Kyung Jeon, Daekee Lee, Sanghyuk Lee, Jaesang Kim

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish
Article number1746553
JournalOncoImmunology
Volume9
Issue number1
DOIs
StatePublished - 1 Jan 2020

Bibliographical note

Funding Information:
We thank T Nakayama and H Hosokawa of Chiba University for providing pw120 plasmids. This work was supported by the National Research Foundation of Korea (NRF-2015K1A4A3047851) funded by the Ministry of Science and ICT, Republic of Korea and by the Technology Innovation Program (10050154) of the Ministry of Trade, Industry and Energy, Republic of Korea.

Publisher Copyright:
© 2020, © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.

Keywords

  • Angioimmunoblastic T-cell lymphoma
  • PD-1
  • RHOA
  • follicular helper T-cell

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