Elucidation of the pathogenesis of HTLV-1-related diseases and exploration of new therapeutic strategies using genetically engineered mice

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09931
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: University of Miyazaki
• Principal Investigator: Kameda Takuro 宮崎大学, 医学部, 助教 (30468029)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ATLL / HBZ / CARD11 / 癌 / シグナル伝達 / ウイルス

Outline of Final Research Achievements

We created and analyzed mouse models of adult T-cell leukemia/lymphoma caused by human T-cell leukemia virus (HTLV-1). HBZ transgenic mice (HBZ-Tg) showed chronic inflammation and lymphadenopathy in about 10% of mice by 48 weeks of age. In mice transduced with a driver mutation, CARD11E626K, about 50% of the mice showed lymphadenopathy at 24 weeks of age. In mice with both HBZ and CARD11E626K, about 70% of the mice showed lymphadenopathy at 24 weeks of age. They also showed infiltration of T-cells into various organs and shortened survival. Based on these models, researches on the pathogenesis of ATL and the novel therapies targeting the driver mutation are ongoing.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

世界では3000万人以上のHTLV-1キャリアが存在すると推定されている。日本国内ではHTLV-1キャリアが約100万人存在し、毎年約1100人がATLを発症している。欧米では日本以上にATL は希少であるため、日本にはATLの基礎研究と治療法開発を遂行する責務がある。本研究でATLの遺伝学的基盤を踏まえて作成されたマウスモデルは、今後の新規治療の開発基盤になりうる成果である。