2018 Fiscal Year Research-status Report
Modeling Angioimmunoblastic T-cell lymphoma in mouse based on its genetic lesions
| Project/Area Number |
18K16077
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Keywords | AITL / RHOA / dasatinib / VAV1 |
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| Outline of Annual Research Achievements |
Angioimmunoblastic T-cell lymphoma (AITL) is a T-cell lymphoma with unfavorable prognosis. Nearly 70% of AITL patients harbored hotspot G17V RHOA accompanied with TET2 mutations. In RHOA-mutation negative patients, VAV1 mutations have been identified. We have made the mouse models mimicking these human AITL genetic lesions. We found that the mice expressing G17V RHOA mutant together with Tet2 deletion developed AITL-like diseases and dasatinib is effective in treatment Balb/c nude mice transplanted with tumour cells derived from these mice. Mice expressed VAV1 mutant showed lung infiltration of lymphocytes but not lymphoma phenotype. However, VAV1 transgenic p53KO mice developed both immature T-cell and mature (lymphoma) tumours while p53KO mice only developed immature T-cell tumour.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
1. We are now submitting the manuscript containing the results of Tet2cKO G17V RHOA mice and dasatinib treatment in these mice.
2. We are analysing the mechanism of tumorigenesis of VAV1 mutations.
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| Strategy for Future Research Activity |
1. Establishment of cell lines from tumour derived from VAV1 transgenic p53KO mice.
2. Transplantation of tumour cells into Balb/c nude mice.
3. Analysis the transcriptome of tumours cells by RNA sequencing to find out the targets of treatment.
4. Treatment of cell lines and transplanted Balb/c nude mice based on the targets found by transcriptome analysis using drug panels.
5. Performing whole exon sequencing for tumours developed from VAV1 transgenic p53KO and p53KOmice to find out the genetic differences.
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[Journal Article] Blastic plasmacytoid dendritic cell neoplasm arising from clonal hematopoiesis2018
Author(s)
Sakurako Suma,Mamiko Sakata-Yanagimoto, Tran B. Nguyen, Keiichiro Hattori, Taiki Sato, Masayuki Noguchi,Yasuhito Nannya, Seishi Ogawa, Rei Watanabe, Manabu Fujimoto,Naoya Nakamura. Manabu Kusakabe, Hidekazu Nishikii, Takayasu Kato, Shigeru Chiba
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Journal Title
International Journal of Hematology
Volume: 108
Pages: 447-451
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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