Modeling Angioimmunoblastic T-cell lymphoma in mouse based on its genetic lesions

2018 年度 実施状況報告書

• 研究課題/領域番号: 18K16077
• 研究機関: 筑波大学
• 研究代表者: NGUYEN BICH・TRAN 筑波大学, 医学医療系, 研究員 (10812901)
• 研究期間 (年度): 2018-04-01 – 2020-03-31
• キーワード: AITL / RHOA / dasatinib / VAV1

研究実績の概要

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.

現在までの達成度 (区分)

2: おおむね順調に進展している

理由

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.

今後の研究の推進方策

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.

研究成果

• [雑誌論文] Blastic plasmacytoid dendritic cell neoplasm arising from clonal hematopoiesis (2018)
  • 著者名/発表者名: 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
  • 雑誌名: International Journal of Hematology 巻: 108 ページ: 447-451
  • DOI: https ://doi.org/10.1007/s1218 5-018-2461-z
  • 査読あり / オープンアクセス / 国際共著
• [学会発表] Effectiveness of Dasatinib in an Angioimmunoblastic T-cell Lymphoma Mouse Model (2018)
  • 著者名/発表者名: Nguyen Bich Tran
  • 学会等名: Japanese Association of Hematology International Symposium
  • 国際学会
• [学会発表] Effectiveness of Dasatinib in a T-cell Lymphoma Mouse Model (2018)
  • 著者名/発表者名: Nguyen Bich Tran
  • 学会等名: Japanese Cancer Association Annual Meeting 2018
  • 国際学会
• [学会発表] Effectiveness of Dasatinib in an Angioimmunoblastic T-cell Lymphoma Mouse Model (2018)
  • 著者名/発表者名: Nguyen Bich Tran
  • 学会等名: Japanese Association of Hematology Annual Meeting 2018
  • 国際学会