| Project/Area Number |
18K15411
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 52010:General internal medicine-related
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| Research Institution | Gunma University |
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Principal Investigator |
Gotoh Nanami 群馬大学, 大学院保健学研究科, 助教 (80782482)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 急性骨髄性白血病 / 酸化ストレス / DNA修復 / APE1 |
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| Outline of Final Research Achievements |
We focused on base excision repair, a DNA repair pathway closely related to oxidative stress, and studied its relationship to the pathogenesis of acute myeloid leukemia (AML). All of the base excision repair genes were highly expressed in the bone marrow of AML patients, with APE1 being the most prominent. Inhibition of APE1 expression significantly reduced the proliferation of AML cells, especially in the knockout strain. The suppression of proliferation was particularly pronounced in the knockout strain, suggesting that APE1 is required for AML cell proliferation. Therefore, it is possible that high APE1 expression contributes to AML malignancy by favoring AML cell survival.
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| Academic Significance and Societal Importance of the Research Achievements |
AMLにおけるAPE1 knockout株の樹立は、我々が知る限りでは未だ報告がない。このため、AMLの病態、特に難治化に対するAPE1の機能的意義について新たな知見が得られると期待される。また、APE1 knockoutによりAML細胞の増殖が著しく抑制されることから、AMLの増殖・生存において、APE1が必要であることがわかった。これらの知見をさらに発展させることにより、APE1という新たな分子を標的としたAMLの治療戦略に結び付けられると考える。
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