| Budget Amount *help |
¥119,990,000 (Direct Cost: ¥92,300,000、Indirect Cost: ¥27,690,000)
Fiscal Year 2009: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2008: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2007: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2006: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2005: ¥51,350,000 (Direct Cost: ¥39,500,000、Indirect Cost: ¥11,850,000)
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| Research Abstract |
We identified leukemia stem cells (LSC) of acute myelogenous leukemia (AML) and chronic lymphocytic leukemia (CLL) using multi-colored FACS and xenotransplant system with severe immune-deficient mice. We identified high expression of TIM-3 in LSC population, but not hematopoietic stem cells (HSC). Treatment with anti-TIM-3 antibody markedly reduced leukemic repopulation, but did not affect reconstitution of normal HSCs. We also found that MCL-1 play a critical role in maintenance of LSC via FLT3 signaling and acquisition of FLT3 abnormality ensures LSC survival by upregulating MCL-1 via constitutive STAT5 activation. We also have shown that primary oncogenic event in CLL involves hematopoietic stem cells, and development of CLL might depend on clonal selection by abnormal BCR signaling mutations follow to become overt CLL.
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