| Budget Amount *help |
¥24,050,000 (Direct Cost: ¥18,500,000、Indirect Cost: ¥5,550,000)
Fiscal Year 2018: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2017: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2016: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
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| Outline of Final Research Achievements |
In the present study, we tried to clarify the function of TIM-3 signaling in human acute myeloid leukemia stem cells. TIM-3 has been originally identified as a T-cell exhaustion marker; however, its function and signaling in leukemic stem cells are still elusive. We identified that galectin-9, a ligand for TIM-3, ligation to TIM-3 recruits HCK to its cytoplasmic tail and HCK is subsequently activated in leukemic stem cells, leading to the activation of canonical Wnt pathway through the interaction with p-120 catenin even in the absence of Wnt ligands. TIM-3 signaling directly activates the canonical Wnt pathway and induces the aberrant beta-catenin accumulation independent of conventional Wnt ligands. Thus, TIM-3 signaling is a novel and specific canonical Wnt pathway regulator in human leukemic stem cells.
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