| Project/Area Number |
24659466
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hematology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KIKUCHI Shohei 札幌医科大学, 医学部, 助教 (80515792)
IYAMA Satoshi 札幌医科大学, 医学部, 助教 (50398319)
KATO Junji 札幌医科大学, 医学部, 教授 (20244345)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | MDS / 8-OHdG / 鉄キレート / 酸化的DNA損傷 / 鉄キレート剤 / 骨髄異形成症候群 / 幹細胞 / 白血病 / HPLC-ECD / 活性酸素 / 予後因子 / ゲノム / 腫瘍幹細胞 |
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| Outline of Final Research Achievements |
Most MDS patients eventually require red RBC transfusions for anemia and consequently develop iron overload. Excess free iron in cells catalyzes generation of reactive oxygen species that cause oxidative stress, including oxidative DNA damage. However, it is uncertain how iron-mediated oxidative stress affects the pathophysiology of MDS. We analyzed 8-OHdG levels in peripheral blood mononuclear cells (PBMC) obtained from MDS patients before and after iron chelator,deferasirox, administration. We showed that the 8-OHdG levels in MDS patients were significantly higher than those in healthy volunteers and were positively correlated with SF and chromosomal abnormalities. Importantly, the 8-OHdG levels in PBMC of MDS patients significantly decreased after deferasirox administration, suggesting that iron chelation reduced oxidative DNA damage. Thus, excess iron could contribute to the pathophysiology of MDS and iron chelation therapy could improve the oxidative DNA damage in MDS patients.
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