| Project/Area Number |
18K07224
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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 50010:Tumor biology-related
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| Research Institution | Fujita Health University (2020)
University of Tsukuba (2018-2019) |
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Principal Investigator |
Sugihara Eiji 藤田医科大学, 共同利用研究設備サポートセンター, 准教授 (50464996)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | MYC / マウスモデル / リンパ腫 / AID / 悪性リンパ腫 / Myc / 治療抵抗性 / BCL2 / 分子標的阻害剤 / DHL |
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| Outline of Final Research Achievements |
The aggressive types of non-Hodgkin's lymphoma, including Burkitt lymphoma and diffuse large B cell lymphoma, is a hematopoietic tumor with a high frequency, and the prognosis is poor if the oncogene MYC is highly expressed due to abnormalities such as translocation and mutation. High expression at the same time as BCL2 shows high refractory and extremely poor prognosis, so the development of a treatment method for MYC abnormal lymphoma is a critical issue. In this study, we conducted comprehensive gene expression profiling, inhibitor screening and whole-genome sequencing using three types of lymphoma mouse models driven by MYC. We identified unreported genes regulated by MYC and involved in lymphoma formation. Database-based analysis revealed that these genes affect the prognosis of lymphoma patients, suggesting functional involvement in lymphoma development. Furthermore, under certain conditions, we showed the possibility of AID introducing mutations that suppress cell death.
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| Academic Significance and Societal Importance of the Research Achievements |
これまでMYCを直接的または間接的に阻害する薬剤の開発が進められてきたが、未だ臨床試験に成功した薬剤はない。本研究成果により新たに同定したMYCが制御する遺伝子やMYCによるリンパ腫形成に関与する遺伝子はMYC異常の難治性リンパ腫に対する阻害剤開発の標的分子になる可能性が高い。またMYCは他の臓器のがんの発症・進展にも関わることが報告されているため、今後、本研究成果が他のがん種へ展開することで波及効果も得られると大いに期待できる。
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