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
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Keywords | ATLL / HBZ / CARD11 / 癌 / シグナル伝達 / ウイルス / PRKCb |
|---|
| 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.
|
| 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。
|
Report
(4 results)
Research Products
(29 results)
-
-
[Journal Article] Clinical significance of soluble CADM1 as a novel marker for adult T-cell leukemia/lymphoma.2020
Author(s)
Nakahata S, Syahrul C, Nakatake A, Sakamoto K, Yoshihama M, Nishikata I, Ukai Y, Matsuura T, Kameda T, Shide K, Kubuki Y, Hidaka T, Kitanaka A, Ito A, Takemoto S, Nakano N, Saito M, Iwanaga M, Sagara Y, Mochida K, Amano M, Maeda K, Sueoka E, Okayama A, Utsunomiya A, Shimoda K, Watanabe T, Morishita K.
-
Journal Title
Haematologica
Volume: 105
Issue: 2
Pages: 1-1
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
[Journal Article] Effects of mogamulizumab in adult T-cell leukemia/lymphoma in clinical practice.2017
Author(s)
Sekine M, Kubuki Y, Kameda T, Takeuchi M, Toyama T, Kawano N, Maeda K, Sato S, Ishizaki J, Kawano H, Kamiunten A, Akizuki K, Tahira Y, Shimoda H, Shide K, Hidaka T, Kitanaka A, Yamashita K, Matsuoka H, Shimoda K
-
Journal Title
European journal of haematology.
Volume: 98
Issue: 5
Pages: 501-507
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
[Presentation] ATL in Miyazaki Prefecture2019
Author(s)
Masaaki Sekine, Yuki Tahira, Keiichi Akizuki, Ayako Kamiunten, Takuro Kameda, Kotaro Shide, Tomonori Hidaka, Yoko Kubuki, Kazuya Shimoda
Organizer
第81回日本血液学会学術集会
Related Report
-
-
-
-
-
[Presentation] マウスモデルを用いたATLLにおけるTET2欠損の役割の検討2018
Author(s)
亀田拓郎, 幣光太郎, 上運天綾子, 大園芳範, 関根雅明, 田平優貴, 秋月渓一, 日髙智徳, 久冨木庸子, 北中明, 下田和哉
Organizer
第5回日本HTLV-1学会学術集会
Related Report
-
[Presentation] 臨床情報とゲノム情報を統合したaggressive ATLの予後予測2018
Author(s)
亀田拓郎, 片岡圭亮, 三好寛明, 幣光太郎, 北中明, 日高道弘, 宇都宮與, 柴田龍弘, 大島孝一, 川誠司, 下田和哉
Organizer
第5回日本HTLV-1学会学術集会
Related Report
-
-
-
[Presentation] TET2 Mutation Associated with Organ Infiltrations in ATLL2018
Author(s)
Kameda T, Shide K, Kamiunten A, Tahira Y, Akizuki K, Sekine M, Hidaka T, Kubuki Y, Hidaka M, Utsunomiya A, Ohshima T, Kataoka K, Ogawa S, Shimoda K
Organizer
60th ASH Annual Meeting and Exposition.
Related Report
Int'l Joint Research
-
-
-
