Elucidation of onset mechanism of bovine leukemia and development of an early diagnosis method based on lymphocyte clonality analysis

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03142
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: The University of Tokyo
• Principal Investigator: Inokuma Hisashi 東京大学, 大学院農学生命科学研究科(農学部), 教授 (70263803)
• Co-Investigator(Kenkyū-buntansha): 芳賀 猛 東京大学, 大学院農学生命科学研究科(農学部), 教授 (20315360)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 牛伝染性リンパ腫 / クローナリティ解析 / リンパ球 / 発症機構 / 診断法

Outline of Final Research Achievements

Immunoglobulin light chain-λ gene based PCR (IgL-PCR) has been developed to improve the diagnostic accuracy of enzootic bovine leukosis (EBL) by detecting clonal abnormalities. The sensitivity and specificity of IgL-PCR for diagnosis were 64.6% and 95.7%, respectively. Combination of IgL-PCR with IgH-PCR has improved diagnostic sensitivity up-to 77.8%. It was demonstrated that this new method was useful to detect abnormal peripheral blood lymphocytes and clinical diagnosis of EBL. A time-course observation of individuals with abnormal clonality revealed that a completely different clone suddenly turned into a tumor at the onset of EBL. In addition, it was suggested that histone modification abnormalities that induce inactivation of tumor suppressor genes and activation of cell division are involved in the progression of EBL from BLV infection to onset.

Free Research Field

獣医学

Academic Significance and Societal Importance of the Research Achievements

本研究成果の新知見として、発がん時のリンパ球クローンの動態異常や発がんにおけるヒストン修飾異常が明らかとなり、ウイルス発がんメカニズムの一端が明らかとなった。また、本研究の成果として牛のBリンパ球クローナリティ解析法の精度が向上し、ひいては、牛伝染性リンパ腫発症の診断精度が向上することとなった。獣医臨床現場での診断が難しい非典型的な牛伝染性リンパ腫を生前に摘発するために応用されることが期待される。