| Project/Area Number |
20K16181
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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 49020:Human pathology-related
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| Research Institution | Tokai University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 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 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | びまん性大細胞型B細胞リンパ腫 / MYC遺伝子 / AICDA/AID / DLBCL |
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| Outline of Research at the Start |
血液がんの一種にびまん性大細胞型B細胞リンパ腫というものが存在する。この病気の中でもMYC遺伝子に異常があるものは特に予後が悪いとされている。この研究はMYC遺伝子に異常があるびまん性大細胞型B細胞リンパ腫の遺伝子学的特徴を明らかにし、最終的には分子標的治療薬(この病気に特異的な効果を有する薬)の開発につなげることを目標としている。
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| Outline of Final Research Achievements |
When Diffuse large B-cell lymphoma has MYC gene rearrangement (MYC-R) and additional BCL2-R and/or BCL6-R, the lymphoma generally has an adverse prognosis and is named a double hit lymphoma (DHL). But recently, some reports showed that there is DHL with good response to usual chemotherapy and favorable prognosis. The adverse prognosis factor of DHL has not been found yet. To find a prognostic biomarker of DHL, we firstly examined DHL cases with gene expression profiling analysis. The gene expression profiling showed that the high expression of AICDA was associated with an adverse prognosis in DHL. Then, we evaluated immunohistochemical expression of AID, the protein product of AICDA, in DHL cases and confirmed that its expression was also associated with an adverse prognosis in DHL. Therefore, AICDA and AID can be a predictor of an adverse clinical outcome in DHL and immunohistochemistry of AID is useful to find DHL-adverse prognosis group.
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| Academic Significance and Societal Importance of the Research Achievements |
Double hit lymphoma(DHL)の中に予後良好な症例も含まれる事が判明してきた一方で、これまでの報告通り、通常の化学療法には反応せず、極めて予後不良な経過を辿るDHLの症例も多く存在する。今回の研究でAICDA/AIDがDHLの予後不良因子であることが解明された為、今後はDHLの診断時に免疫組織化学的にAID発現を確認することでDHLの予後予測が可能になる。更に、AICDA/AIDを標的とした分子標的薬が開発され、DHLの予後改善につながると考えられる。
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