| Project/Area Number |
15K09468
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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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| Research Field |
Hematology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
ARAI Ayako 東京医科歯科大学, 大学院保健衛生学研究科, 准教授 (70359678)
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| Co-Investigator(Kenkyū-buntansha) |
今留 謙一 国立研究開発法人国立成育医療研究センター, 高度感染症診断部, 部長 (70392488)
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| Co-Investigator(Renkei-kenkyūsha) |
OHARA Osamu 公益財団法人かずさDNA研究所, ゲノム医療推進部, 部長 (20370926)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | EBV陽性T,NKリンパ増殖症 / EBウイルス / NF-ｋB / bortezomib / APOBEC3B / NF-kB / EBV陽性T、NK細胞リンパ増殖症 / Epstein-Barr Virus / NF-κB / Bortezomib / P糖蛋白 |
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| Outline of Final Research Achievements |
Chronic active EBV infection (CAEBV) is a neoplasm of EBV-infected T- or NK-cells. It was newly defined as a disorder including conventional CAEBV, severe mosquito bite allergy, and hydroa vacciniforme-like lymphoproliferative disorder according to the WHO classification of lymphoid neoplasms revised in 2017. CAEBV is resistant to chemotherapies, and the only curative treatment strategy thus far has been hematopoietic stem cell transplantation. We found that APOBEC3B expression was increased in the EBV-positive T- or NK-cell lines cells from patients of CAEBV, one of EBV-positive T or NK-cell lymphoproliferative diseases. A proteasome inhibitor, bortezomib suppressed APOBEC3B expression in these cells and inhibited proliferation and cytokine production in these cells. In addition, bortezomib administration decreased EBV-DNA load in the peripheral blood of CAEBV xenograft models. Based on the results, we started an investigator-initiated clinical research of bortezomib for CAEBV.
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