Angioimmunoblastic T-cell lymphoma-like lymphadenopathy in mice transgenic for human RHOA with p.Gly17Val mutation
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 f...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-01-01
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| Series: | OncoImmunology |
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| Online Access: | http://dx.doi.org/10.1080/2162402X.2020.1746553 |
| _version_ | 1818928144948658176 |
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| author | Gyu Jin Lee Yukyung Jun Hae Yong Yoo Yoon Kyung Jeon Daekee Lee Sanghyuk Lee Jaesang Kim |
| author_facet | Gyu Jin Lee Yukyung Jun Hae Yong Yoo Yoon Kyung Jeon Daekee Lee Sanghyuk Lee Jaesang Kim |
| author_sort | Gyu Jin Lee |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T03:24:15Z |
| format | Article |
| id | doaj.art-3d17cc0133224f0a988ebdea88222e0b |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-20T03:24:15Z |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-3d17cc0133224f0a988ebdea88222e0b2022-12-21T19:55:08ZengTaylor & Francis GroupOncoImmunology2162-402X2020-01-019110.1080/2162402X.2020.17465531746553Angioimmunoblastic T-cell lymphoma-like lymphadenopathy in mice transgenic for human RHOA with p.Gly17Val mutationGyu Jin Lee0Yukyung Jun1Hae Yong Yoo2Yoon Kyung Jeon3Daekee Lee4Sanghyuk Lee5Jaesang Kim6Ewha Womans UniversityEwha Womans UniversitySungkyunkwan UniversitySeoul National University College of MedicineEwha Womans UniversityEwha Womans UniversityEwha Womans UniversityA 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.http://dx.doi.org/10.1080/2162402X.2020.1746553angioimmunoblastic t-cell lymphomarhoafollicular helper t-cellpd-1 |
| spellingShingle | Gyu Jin Lee Yukyung Jun Hae Yong Yoo Yoon Kyung Jeon Daekee Lee Sanghyuk Lee Jaesang Kim Angioimmunoblastic T-cell lymphoma-like lymphadenopathy in mice transgenic for human RHOA with p.Gly17Val mutation OncoImmunology angioimmunoblastic t-cell lymphoma rhoa follicular helper t-cell pd-1 |
| title | Angioimmunoblastic T-cell lymphoma-like lymphadenopathy in mice transgenic for human RHOA with p.Gly17Val mutation |
| title_full | Angioimmunoblastic T-cell lymphoma-like lymphadenopathy in mice transgenic for human RHOA with p.Gly17Val mutation |
| title_fullStr | Angioimmunoblastic T-cell lymphoma-like lymphadenopathy in mice transgenic for human RHOA with p.Gly17Val mutation |
| title_full_unstemmed | Angioimmunoblastic T-cell lymphoma-like lymphadenopathy in mice transgenic for human RHOA with p.Gly17Val mutation |
| title_short | Angioimmunoblastic T-cell lymphoma-like lymphadenopathy in mice transgenic for human RHOA with p.Gly17Val mutation |
| title_sort | angioimmunoblastic t cell lymphoma like lymphadenopathy in mice transgenic for human rhoa with p gly17val mutation |
| topic | angioimmunoblastic t-cell lymphoma rhoa follicular helper t-cell pd-1 |
| url | http://dx.doi.org/10.1080/2162402X.2020.1746553 |
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