2019 Fiscal Year Final Research Report
Elucidation of the pathogenesis of HTLV-1-related diseases and exploration of new therapeutic strategies using genetically engineered mice
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 |
|
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。
|