Unraveling the regression mechanisms of methotrexate-associated lymphoproliferative disorders through rheumatoid arthritis-related genes

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K17845
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: DOBASHI Akito 公益財団法人がん研究会, がん研究所 分子標的病理プロジェクト, 研究員 (40772249)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: びまん性大細胞型B細胞リンパ腫 / マルチ遺伝子パネル検査 / 医原性免疫不全関連リンパ増殖性疾患 / メトトレキサート / 自然退縮

Outline of Final Research Achievements

Iatrogenic immunodeficiency-associated lymphoproliferative disorders (IIALPDs) exhibit diverse histological findings, ranging from reactive lymphadenitis to lymphoma. Approximately 60% of cases show spontaneous regression following the reduction or discontinuation of immunosuppressive agents. This study conducted a comprehensive genetic analysis of 54 cases with the histology type of diffuse large B-cell lymphoma (DLBCL), comparing those with spontaneous regression to those requiring chemotherapy. The analysis revealed characteristic genetic alterations in DLBCL, with SGK1 and TET2 variants observed in spontaneous regression cases, while major somatic variants were absent. These findings suggest that multi-gene panel testing at diagnosis is crucial for determining early therapeutic intervention or the cessation of implicated medications in the management of IIALPDs.

Free Research Field

血液腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究は、医原性免疫不全関連リンパ増殖性疾患(IIALPD)において、自然退縮例と化学療法必要例の遺伝子変化の違いを明らかにした。化学療法必要例では、びまん性大細胞型B細胞リンパ腫（DLBCL）に特徴的な遺伝子変化が認められ、自然退縮例では主要な体細胞バリアントが欠如していた。この発見は、IIALPDの診断時にマルチ遺伝子パネル検査を行うことで、早期の治療介入や関連薬剤の中止の判断に役立つことを示唆している。