| Project/Area Number |
18K08336
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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 | Jichi Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
古川 雄祐 自治医科大学, 医学部, 教授 (00199431)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 多発性骨髄腫 / APOBEC3B / MGUS / 点突然変異 / APOBEC3 |
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| Outline of Final Research Achievements |
We tested the hypothesis that the APOBEC3 gene promotes the progression of multiple myeloma. Among the APOBEC3 family of cytidine deaminases, the APOBEC3B gene (A3B) was specifically and strongly expressed in myeloma cells; furthermore, abnormal A3B mRNA, which retains intron 7, (A3Bi7) was expressed in myeloma cell lines. When A3Bi7 and wild-type A3B cDNA were introduced into 293 cells, GC>AT point mutations were more frequently observed in the TP53 gene in A3Bi7-trnasduced cells. Anti-myeloma drugs induced the expression of A3Bi7 mRNA and proteins, suggesting that A3Bi7 is involved in the acquisition of gene mutations, which may underlie clonal evolution of residual myeloma cells after treatments.
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| Academic Significance and Societal Importance of the Research Achievements |
APOBEC3遺伝子の質的・量的異常が、癌関連遺伝子の点突然変異やゲノムの不安定性を惹起し、多発性骨髄腫の進展・増悪に寄与する可能性を明らかにした。多発性骨髄腫は治療薬の進歩にも関わらず依然難治性であり、本研究成果により骨髄腫の進展・増悪予測としての標的遺伝子の一つが同定され、今後創薬研究開発へも繋がると思われる。
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