Development of an algorithm for differentiation of cutaneous ATL from non-viral skin lymphoma by combined extraction of pathologically relevant gene clusters.

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17354
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: University of the Ryukyus
• Principal Investigator: Miyagi Takuya 琉球大学, 医学(系)研究科(研究院), 助教 (00631988)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 成人T細胞白血病リンパ腫 / 皮膚リンパ腫 / 菌状息肉症 / 新規人工知能 / トランスクリプトーム解析 / 鑑別アルゴリズム

Outline of Final Research Achievements

After reviewing the pathology specimens used for diagnosis in conventional dermatological practice, including their clinical course, we selected and submitted specimens that could be determined to be typical cutaneous adult T-cell leukemia-lymphoma with HTLV-1 virus copy number per cell of 10 copies /100 cells or more. RNA was extracted from the selected tissues and used as a substrate for a transcriptome library to obtain raw data for comprehensive gene expression. At this point, due to the small number of specimens, we have not yet been able to identify statistically significant genetic groups with large differences in gene expression, but based on previous reports, we have selected several candidate genes. In the future, we would like to increase the number of samples and identify genes that we believe are important for differentiation.

Free Research Field

皮膚科

Academic Significance and Societal Importance of the Research Achievements

ATLの診断はサザンブロット法によるプロウイルスの単クローン性の組み込みを確認する。しかし、HTLV-1のプロウイルスが単クローン性に組み込まれているものの、病変部組織の遺伝子発現パターンは未分化大細胞リンパ腫と一致し、実際にATLの治療に反応せず死亡した症例を経験した。このように、HTLV-1キャリアに生じたATL以外の皮膚リンパ腫をATLとしてしまう危険性が残っている。本課題では、各リンパ腫を鑑別しうる、サザンブロット法に変わる病理学的な診断マーカーを特定し、診断アルゴリズムを確立し、さらに腫瘍化機序に直結する遺伝子発現や、ドライバー変異が特定できれば、治療法の開発にも直結する。