| Budget Amount *help |
¥181,480,000 (Direct Cost: ¥139,600,000、Indirect Cost: ¥41,880,000)
Fiscal Year 2014: ¥33,020,000 (Direct Cost: ¥25,400,000、Indirect Cost: ¥7,620,000)
Fiscal Year 2013: ¥34,450,000 (Direct Cost: ¥26,500,000、Indirect Cost: ¥7,950,000)
Fiscal Year 2012: ¥35,880,000 (Direct Cost: ¥27,600,000、Indirect Cost: ¥8,280,000)
Fiscal Year 2011: ¥35,620,000 (Direct Cost: ¥27,400,000、Indirect Cost: ¥8,220,000)
Fiscal Year 2010: ¥42,510,000 (Direct Cost: ¥32,700,000、Indirect Cost: ¥9,810,000)
|
|---|
| Outline of Final Research Achievements |
Most cancer stem cells (CSCs) are quiescent, and this characteristic provides these cells with resistance to conventional anticancer therapies that preferentially target dividing cells. CSCs that persist in spite of therapies may result in relapses and metastases. Here we show that Fbxw7 and p57 play a pivotal role in maintenance of quiescence in leukemia-initiating cells (LICs) of chronic myeloid leukemia (CML). Our findings reveal that ablation of Fbxw7 or p57 in a mouse model of CML results in disruption of quiescence in LICs. Furthermore, we demonstrate that LICs lacking Fbxw7 or p57 are sensitive to currently available anticancer drugs and combination therapy with Fbxw7/p57 depletion and these drugs is able to eradicate LICs, leading to a decreased relapse rate and a significant survival advantage. Such combination therapy is also effective for human CML LICs, supporting our conclusion that Fbxw7 and p57 are promising targets for the treatment of human leukemia.
|
