| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2017: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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| Outline of Final Research Achievements |
Hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs) have self-renewal ability to maintain normal hematopoiesis and leukemia propagation, respectively. Recently, it has been reported that bone forming osteoblasts provide a microenvironment for LSCs and are implicated in pathogenesis and progression of leukemia as an osteoblastic niche in bone marrow. We here show a critical role of mTORC1 in regulating normal hematopoiesis and leukemia progression through its expression in osteoblasts in mice. Using a mouse models of acute myeloid leukemia (AML), we revealed that AML cells enhance the mTORC1 activity in osteoblasts in vivo and in vitro. Subsequent analyses determined that inactivation of Tsc1, a negative regulator of mTORC1, in osteoblasts results in a marked acceleration of AML. These findings highlight a critical role of mTORC1 in normal hematopoiesis and leukemia propagation, at least in part, through its expression in osteoblastic niche.
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