Function of APOBEC3 in EBV-positive T or NK-cell lymphoproliferative diseases

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09468
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Tokyo Medical and Dental University
• 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)
• 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)
• 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)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: EBV陽性T,NKリンパ増殖症 / EBウイルス / NF-ｋB / bortezomib / APOBEC3B

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.

Free Research Field

医歯薬学