| Project/Area Number |
16H05340
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | Kyushu University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
菊繁 吉謙 九州大学, 医学研究院, 講師 (40619706)
赤司 浩一 九州大学, 医学研究院, 教授 (80380385)
|
|---|
| Project Period (FY) |
2016-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2019: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
|
|---|
| Keywords | TIM-3 / 白血病幹細胞 / Wnt pathway / β-catenin / T細胞性腫瘍 / 白血病 / T-ALL |
|---|
| Outline of Final Research Achievements |
TIM-3 is a leukemia stem cell (LSC)-specific surface molecule that is essential for maintaining the self-renewal capacity of LSCs. In the present study, we comprehensively analyzed the signaling molecules involved in the signal transduction of LSCs, and found that TIM-3 could activate canonical Wnt pathway independent of Wnt ligands via several LSCs-specific mechanisms. Furthermore, we compared TIM-3 signaling outcome between human TIM-3+ exhausted T cell and TIM-3+ LSCs, and found that LSCs, but not exhausted T cells, efficiently activate canonical Wnt pathway via the interaction between TIM-3 and galectin-9, a TIM-3 ligand. This study provides the novel evidence that TIM-3 represents a novel canonical Wnt pathway activator specifically utilized in LSCs.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究の遂行により、ヒト白血病幹細胞特異的なTIM-3シグナルの下流分子群を初めて明らかにすることができた。TIM-3シグナルはヒト白血病幹細胞の幹細胞性維持に必須のシグナルであることから、抗体によるTIM-3分子を直接標的とする治療戦略に加えて、本研究で同定した下流シグナル分子群は小分子化合物を用いたTIM-3シグナル阻害という新しい治療戦略の重要な治療標的分子候補である。したがって、ヒト白血病幹細胞を特異的に標的とする新規治療法確立するために本研究の果たした意義は非常に大きいものと考えられる。
|
