| Budget Amount *help |
¥45,110,000 (Direct Cost: ¥34,700,000、Indirect Cost: ¥10,410,000)
Fiscal Year 2015: ¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000)
Fiscal Year 2014: ¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000)
Fiscal Year 2013: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
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| Outline of Final Research Achievements |
In this study, we have identified common machinery for the development and maintenance of myeloid leukemic stem cells; TIM-3/galectin-9 autocrine loop. CD34+CD38-TIM-3+ myeloid leukemic stem cells produce and secrete galectin-9, TIM-3 ligand in an autocrine manner, leading to the constitutive activation of TIM-3 signaling. TIM-3 signaling promotes self-renewal capacity of the malignant stem cells via co-activation of NF-kB and beta-catenin pathways. Thus, signaling molecules downstream of TIM-3 and galectin-9 ligation, as well as surface TIM-3 itself might be good candidates for cancer stem cell-target therapy common to most myeloid malignancies. In addition to the identification of TIM-3/galectin-9 autocrine loop, we established the novel immunodeficient mice lines; BRGS and BRGSK mice. Human normal and malignant hematopoiesis could be efficiently reconstituted in the novel immunodeficient mice.
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