Aberrant DNA methylation analysis and development of highly specific risk markers in HTLV-1-related diseases

• Project/Area Number: 18K07267
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Hokuriku University
• Principal Investigator: Sato Hiaki 北陸大学, 医療保健学部, 准教授 (70362960)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: 成人T細胞白血病/リンパ腫(ATL) / DNAメチル化異常 / ヒトT細胞白血病ウイルス1型(HTLV-1) / DNA異常メチル化 / 成人T細胞白血病/リンパ腫 / HTLV-1

Outline of Final Research Achievements

Adult T-cell leukemia/lymphoma (ATL) is a highly refractory disease caused by HTLV-1 infection. In this study, we obtained new insights into the pathogenesis of carrier-to-ATL by analyzing DNA methylation abnormalities in peripheral blood samples from HTLV-1 carriers and ATL patients using the MSP method.
The results of this study indicate that accumulation of DNA methylation abnormalities triggers the development of ATL and that increased DNA methylation abnormalities are associated with progression of the disease stage. This suggests that DNA methylation abnormalities have high clinicopathological significance and may be a predictive marker of disease onset and a target for targeted therapy.

Academic Significance and Societal Importance of the Research Achievements

DNAメチル化異常の蓄積はATLの発症や病的進行に深く関わることが示されたことから、DNAのメチル化異常を標的にしたATLの予防法の開発や新規治療法の可能性が見出された。また、今回選定された8つの遺伝子のDNAメチル化異常を解析することで、ATLを発症する5%のキャリアを早期に検出する指標としても応用できると考えている。