Elucidation of immune abnormalities in thymoma and related autoimmune diseases through comprehensive genetic analysis of T cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16302
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Shinshu University
• Principal Investigator: Kawakami Toru 信州大学, 医学部附属病院, 医員 (50867041)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: クローン性造血 / 胸腺腫 / 赤芽球癆

Outline of Final Research Achievements

We selected 52 genes to be analyzed based on our previous research. We used DNA extracted from the blood of a total of 132 patients with thymoma and related autoimmune diseases. As a result, mutations in genes related to clonal hematopoiesis (a phenomenon in which genetic mutations related to blood cancer are also observed in healthy people) were observed at a high frequency. Patients with mutations in clonal hematopoiesis-related genes were more likely to relapse after treatment. Additionally, some of these mutated genes lose their mutations over time, or conversely acquire new mutations, which are thought to be related to refractoriness.

Free Research Field

血液学

Academic Significance and Societal Importance of the Research Achievements

今回、我々は胸腺腫と、合併する自己免疫疾患、主に赤芽球癆における遺伝子変異の詳細を明らかにした。クローン性造血は血液がんのみならず、心血管疾患、再生不良性貧血などとも関連があるとされるが、胸腺腫や赤芽球癆でも関連があることが示唆された。また、一部のクローン性造血関連遺伝子の変異は患者の治療抵抗性に関連していたが、これらの遺伝子が胸腺腫や、関連する自己免疫疾患の新たな治療標的の候補となる可能性も考えられた。