| Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2014: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2013: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2012: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
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| Outline of Final Research Achievements |
We have reported that plasminogen activator inhibitor-1 (PAI-1), a negative regulator of the fibrinolytic pathway, expressed in the BM niche and negatively regulated the hematopoietic regeneration in the BM microenvironment. Pharmacological inhibition of PAI-1 activity significantly improved hematopoietic recovery after hematopoietic stem cell transplantation. In this study, we demonstrated several evidences about the relationship leukemia and PAI-1. First, leukemia stem cells highly expressed the PAI-1. Second, PAI-1-expressinng leukemia showed resistance to anti-tumor therapy. Finally, co-administration of leukemia-specific molecular target drug and PAI-1 inhibitor facilitated anti-tumor effects. Our results indicate that the inhibition of PAI-1 activity could be a therapeutic approach to eliminate the therapy-resistant leukemia stem cells.
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