| Project/Area Number |
18K15098
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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) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥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 / DLBCL / MYC / NGS / Oncoscan / GEP / MYC遺伝子 / ＤＬＢＣＬ |
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| Outline of Final Research Achievements |
We performed integrated genetic analysis for 23 cases of Diffuse large B-cell lymphoma with MYC rearrangement. Twenty-three cases are composed of 13 cases of double hit lymphoma having MYC and BCL2/BCL6 rearrangements and 10 cases of single hit lymphoma having only MYC rearrangement.
We subdivided our cases into 10 cases with good prognosis group and 13 cases with bad prognosis group for comparative investigation. Good prognosis group showed complete response without relapse for long term by conventional chemotherapy. Bad prognosis group were dead due to lymphoma. Genetically, gain of 1q,3q and 12chr, loss of 1p and 15q were common in bad prognosis group by copy number alteration analysis. High frequency of mutation were seen in MYC and BCL2 in bad prognosis by next generation target sequence analysis. High expression of some genes were seen in bad prognosis group by gene expression profiling analysis.
We think that these findings would lead to development of molecular target drug.
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| Academic Significance and Societal Importance of the Research Achievements |
MYC転座を有するDouble hit lymphomaとSingle hit lymphomaは予後不良とされているが、従来の化学療法で長期寛解に至る予後良好群も存在することが分かった。更に、予後良好群に比して予後不良群ではHans分類でnon-GCBが多く、コピー数変化や変異、発現に差のある遺伝子を複数認めた。
これらの予後良好群と予後不良群の間にみられた異なる所見の中に従来の化学療法に対する反応を規定する変化が存在する可能性がある。特に差異のみられた遺伝子については、発現する蛋白質を解析する事で分子標的薬の開発につながると考えられる。
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