Molecular biological study of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16461
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Shiga University of Medical Science (2021); National Center for Child Health and Development (2020)
• Principal Investigator: Sakamoto Kenichi 滋賀医科大学, 医学部, 助教 (20782048)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: EBウイルス / 血球貪食性リンパ組織球症 / EBウイルス関連血球貪食性リンパ組織球症 / 全ゲノム解析

Outline of Final Research Achievements

The aim of this study is to elucidate new prognostic factors for EBV-HLH by integrating genomic abnormalities and clinical information using whole genome sequence (WGS) of 48 EBV-HLH cases enrolled in HLH-2004. We began WGS of 23 of the 48 EBV-HLH cases for which we had confirmed sufficient sample volume for WGS. In all 23 cases analyzed by WGS, the average amount of EBV-DNA at the onset of EBV-DNA was 357,626 copies/ml in white cell blood and 1,793,562 copies/ml in plasma in all 23 cases analyzed, and T-cell receptor clonality was positive in 14 cases. As soon as the results of WGS are obtained, we will be integrated with clinical information and laboratory values. Finally, we will explore new prognostic factors and therapeutic targets for EBV-HLH.

Free Research Field

血液腫瘍

Academic Significance and Societal Importance of the Research Achievements

EBV-HLHは軽症例から重症例までさまざまな重症度の症例が存在する。これまで重症度や治療反応性を決定する因子についてさまざまな検討がなされてきたが、網羅的ゲノム解析技術を用いてEBV-HLHの中心的役割を果たすクローン化したリンパ球のゲノム異常およびホスト側のバリアントを検討した報告は認められない。EBV-HLH発症の背景にあるゲノム異常を明らかにすることは、幅広い臨床像を示す本疾患の病態を明らかにするだけでなく、適切なリスク分類が可能となることにより適切な治療選択を可能とするため、その意義は非常に高いと思われる。