2020 Fiscal Year Final Research Report
Targeting circadian clock genes in leukemia treatment
| Project/Area Number |
18K08362
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
菊繁 吉謙 九州大学, 医学研究院, 講師 (40619706)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 急性骨髄性白血病 / 概日リズム因子 / クロマチン修飾酵素 |
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| Outline of Final Research Achievements |
The translocation of MLL gene is one of the most frequent chromosomal abnormalities in acute
leukemia. More than 70 genes have been characterized as partner genes. Among them, MLL-AF6 AML patients present with a dismal clinical prognosis due to resistance to initial chemotherapy and high rate
of relapse. We demonstrated that circadian clock gene SHARP1 is expressed solely in MLL-AF6 AML, and its deletion delays the development of leukemia and attenuated leukemia-initiating potential in mouse model. We elucidated molecular role of SHARP1 in MLL-AF6 AML, which could help develop new therapies.
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| Free Research Field |
血液内科学
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| Academic Significance and Societal Importance of the Research Achievements |
白血病発症における概日リズム遺伝子の関与が示唆されてきたが、その分子機構の研究は網羅的には行われていない。本研究で、過去に白血病への関与が報告されていないSHARP1が、白血病MLL融合蛋白との、ヒストン修飾、クロマチン構造へ作用し、白血病発症・維持へ重要な役割を果たしていることを明らかにでき、学術的に極めて興味深い。若年者に発症する難治性の白血病の病態の分子基盤を一つずつ明らかにしていくことは、病気に苦しむ患者に福音をもたらす治療法開発の一助となることが期待される。
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