2023 Fiscal Year Final Research Report
ADAMTS13 gene polymorphism genome editing creation of vascular endothelial cells and exploration for new leukemia therapies
| Project/Area Number |
21K08427
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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 | Aichi Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
花村 一朗 愛知医科大学, 医学部, 教授 (70440740)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 白血病 / ゲノム編集 |
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| Outline of Final Research Achievements |
This study analyzed TLR and ADAMTS13 gene polymorphisms in allogeneic hematopoietic stem cell transplantation. The UNC-93B1 polymorphism rs308328 significantly affected disease-free survival rates post-transplantation. The ADAMTS13 polymorphism rs2285489 was linked to reduced leukemia relapse, but attempts to modify endothelial cells through genome editing were unsuccessful. Introducing the FLT3-ITD gene into K562 cells using CRISPR-Cas9 increased CD52 expression, and alemtuzumab induced specific ADCC in these cells. ARK5 gene knockout in multiple myeloma cells caused mitochondrial fusion, unlike the fission seen in wild-type cells, highlighting ARK5's role in mitochondrial dynamics. These findings reveal critical genetic factors affecting transplant outcomes and suggest new therapeutic targets for leukemia and other malignancies.
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| Free Research Field |
血液内科
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、同種造血幹細胞移植における遺伝子多型の影響を解明し、移植後の無病生存率や白血病再発抑制に関連する遺伝子を特定した。特に、UNC-93B1およびADAMTS13遺伝子多型の解析により、移植後の治療効果予測と個別化医療の実現に貢献する可能性がある。また、FLT3-ITD遺伝子の導入やARK5遺伝子のノックアウトにより、新規治療標的を発見し、白血病および多発性骨髄腫の治療法開発に資する重要な知見を提供した。これらの成果は患者の予後改善に直結し、将来的な治療法の進展に寄与することが期待される。
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