Elucidation of the pathogenesis of adult T-cell leukemia using chromatin structural data at various levels of hematopoietic differentiation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16740
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Tanaka Azusa 東京大学, 大学院医学系研究科(医学部), 特別研究員 (70749796)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 成人T細胞白血病ウイルス / エピゲノム

Outline of Final Research Achievements

Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia-lymphoma (ATL). The leukemic cells typically have a CD4+ memory T cell phenotype, but the mechanisms underlying this process are not presently understood. To clarify the mechanism of leukemia development, we focused on the chromatin structure, which is a central mechanism of cell regulation, and investigated the characteristics of ATL cells. We first developed a method for comparative analysis between samples. Next, we analyzed the chromatin accessibility landscape of HTLV-1-infected cells from ATL cases by comparing the ATAC-seq data with those from 13 types of hematopoietic cells from healthy donors using this method. It was found that in some cases, although ATL is a T-cell leukemia, the chromatin structure resembled to that of myeloid cells, suggesting the possibility of the existence of "T-cell leukemia cells with traits similar to those of myeloid cells".

Free Research Field

エピゲノム

Academic Significance and Societal Importance of the Research Achievements

HTLV-1は母子感染するレトロウイルスで、数千年前から人類と共存してきた。感染者の90%は無症候のまま健康状態を保っているが、感染者の5%は成人T細胞白血病 (ATL) として知られる難治性の白血病やリンパ腫を発症する。HTLV-1は造血幹細胞を含め様々な細胞に感染し、さらに感染を維持したまま分化することが報告されているが、ATL発症メカニズムの関しては未だ不明な点も多い。本研究課題では健常人由来の細胞とのクロマチン構造の比較解析により、T細胞以外の要素を有するATL症例の存在が示唆された。