2017 Fiscal Year Final Research Report
Development of a novel strategy to cancel and prevent the drug resistance in myelodysplastic syndromes
| Project/Area Number |
16K19186
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Applied pharmacology
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Keywords | アザシチジン / テリフルノミド / 薬剤耐性 / 骨髄異形成症候群 |
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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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| Free Research Field |
薬理学、腫瘍学
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