|Budget Amount *help
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2011: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
|Outline of Final Research Achievements
We have previously reported that T-cell immunoglobulin mucin-3 (TIM-3) is expressed on surface of self-renewing leukemic stem cells (LSCs) in acute myeloid leukemia (AML). In this study, we focused on TIM-3 ligands including galectin-9 and HMGB-1 to clarify the function of TIM-3 in human AML. Here, we show that TIM-3 and its ligand, galectin-9, constitutes an autocrine loop critical for human AML LSC development; galectin-9 is highly expressed in primary AML/LSCs, and these AML/LSCs secrete galectin-9 in an autocrine manner. Furthermore, we found that TIM-3/galectin-9 interaction induced the activation of NF-kB pathway in primary TIM-3+ AML cells. These results collectively suggest that TIM-3 and galectin-9 constitutes very unique autocrine stimulatory signaling machinery, which should contribute to the cell autonomous activation of NF-kB pathway in primary AML/LSCs.