| Project/Area Number |
26860740
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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 |
Hematology
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| Research Institution | Nippon Medical School |
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Principal Investigator |
TAMAI HAYATO 日本医科大学, 医学部, 講師 (40465349)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | MLL / AF4 / Amlexanox / S100A6 / ALL / leukemia / GVL / P53 / S100a6 / 急性リンパ性白血病 / ＴＮＦ / ＧＶＬ |
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| Outline of Final Research Achievements |
MLL/AF4-positive ALL is associated with a poor prognosis even after allogeneic hematopoietic stem cell transplantation. We have reported that this ALL shows resistance to TNF-α, which is the factor in the GVL effect or tumor immunity, by upregulation of S100A6 expression followed by interference with the p53-caspases pathway. It was reported that Amlexanox, an anti-allergic drug, inhibited translocation pathway of endogenous S100A6 in endothelial cells.The purpose of this study is to examine the effect of Amlexanox on MLL/AF4-positive ALL. We found Amlexanox significantly inhibited S100A6 expression in the presence of TNF-αin MLL/AF4-positive ALL cells. Amlexanox blocked upregulation of S100A6 expression followed by interference with the p53-caspases pathway. In vivo analysis, MLL/AF4-positive transgenic mice fed a diet containing Amlexanox developed significantly less leukemia at the age of 1 year. These findings suggest that Amlexanox may be a breakthrough of MLL/AF4-positive ALL.
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