| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
Previous studies showed that downregulation of pyrimidine salvage underlies resistance against 5-azacytidine (AZA), indicating an important role for de novo pyrimidine synthesis in AZA resistance. Because de novo pyrimidine synthesis is inhibited by the immunomodulator teriflunomide and its pro-drug leflunomide, we examined the effect of combined treatment with AZA and teriflunomide on AZA resistance to develop a novel strategy to cancel AZA resistance.
Teriflunomide remarkably inhibited the growth of AZA-resistant human leukemia cell lines in comparison with their AZA-sensitive counterparts and activated pyrimidine salvage in AZA-resistant cells. In the presence of a non-toxic concentration of teriflunomide, AZA induced apoptosis in AZA-resistant cells and leukemia cells from AZA-resistant patients.
These results suggest that combined treatment with AZA and teriflunomide can be a novel strategy to overcome AZA resistance.
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