| Project/Area Number |
18K15392
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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 | Kyushu University |
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Principal Investigator |
Kimura Tomoko 九州大学, 医学研究院, 助教 (20632772)
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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 | 概日リズム / 急性白血病 / CK2 / ミトコンドリア代謝 / 白血病 / ミトコンドリア / GO289 / 急性骨髄性白血病 / 概日リズム調節因子 / 造血幹前駆細胞 / MLL-AF９白血病マウスモデル / 抗腫瘍効果 / 概日リズム調節因子（Period, Cry） / がん幹細胞 |
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| Outline of Final Research Achievements |
In human and mouse hematologic tumor cell lines, inhibition of circadian rhythm regulators with the new compound had a growth inhibitory effect and loss or prolongation of circadian rhythm was observed in the spleen and bone marrow of leukemic mice. Gene expression analysis showed that factors related to mitochondrial function were significantly decreased. It was suggested that the anti-tumor effect may be caused by induction of metabolic and proliferative inhibition by reducing mitochondrial function in leukemia cells.
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| Academic Significance and Societal Importance of the Research Achievements |
地球上に生息するほぼすべての生物が有する概日リズムは、様々な疾患の発病との関連が報告されている。我々は概日リズム調節因子を抑制する新規化合物が、抗白血病効果を持つことを示し、概日リズムと急性骨髄性白血病（AML）を直接関連付ける新たな作用機序の一端を解明した。現在使用されている抗がん剤とは異なる作用点を持つ、より選択性の高い抗白血病治療薬となる可能性が示唆された。
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