Analysis of genomic and epigenomic regulatory mechanisms that determine abnormal characteristics of HTLV-1-infected cells in HAM.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03575
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Yamano Yoshihisa 聖マリアンナ医科大学, 医学部, 教授 (80445882)
• Co-Investigator(Kenkyū-buntansha): 山岸 誠 東京大学, 大学院新領域創成科学研究科, 特任講師 (90625261)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: HAM / HTLV-1 / エピゲノム / ゲノム変異 / クローン構造

Outline of Final Research Achievements

The aim of this study was to elucidate the genomic and epigenomic control mechanisms that determine abnormal characteristics of HTLV-1-infected cells in HTLV-1-associated myelopathy (HAM). First, we elucidated viral mutation information in HAM patients（Cell Rep, 29(3):724-735, 2019）. In addition, by analyzing the clonality and somatic mutation of HTLV-1-infected cells in HAM patients, we found that HAM patients have a high incidence of HTLV-1-induced leukemia (ATL), and HAM patients with HTLV-1-infected cells undergoing clonal expansion with somatic mutation characteristic of ATL have an extremely high risk of ATL（Proc Natl Acad Sci USA, 117(21): 11685-11691, 2020）.

Free Research Field

脳神経内科学、ウイルス免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究により得られたゲノム、エピゲノム、遺伝子発現、ウイルスデータを多層データとして統合し、HAM発症に至る異常を階層的に整理することで、HAM発症の根本原因の理解や、より効果的な治療法の開発に繋がる分子基盤が創出された。また、本研究により得られた知見はHAM患者におけるATL発症リスク診断法の確立という臨床的に重要な課題の解決に結びつく成果となった。