2022 Fiscal Year Final Research Report

Functional analysis of novel responsible genes for methotrexate-related lymphoproliferative disease toward genomic medicine

Research Project

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Project/Area Number	20K07384
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 49020:Human pathology-related
Research Institution	National Hospital Organization Osaka-Minami Medical Center
Principal Investigator	Hoshida Yoshihiko 独立行政法人国立病院機構(大阪南医療センター臨床研究部), その他部局等, 医長 (40324777)
Co-Investigator(Kenkyū-buntansha)	大島至郎独立行政法人国立病院機構(大阪南医療センター臨床研究部), その他部局等, 部長 (50362728) 大前陽輔国立研究開発法人国立国際医療研究センター, その他部局等, 上級研究員 (70722552) 西尾和人近畿大学, 医学部, 教授 (10208134) 坂井和子近畿大学, 医学部, 講師 (20580559) 冨田裕彦国際医療福祉大学, 医学部, 教授 (60263266)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	Rheumatoid arthritis / LPD / Methotrexate / RNA transcriptome / GWAS / MTX-LPD / RA-LPD
Outline of Final Research Achievements	Lymphoproliferative disorders (LPD) that develop in patients with rheumatoid arthritis (RA) treated with low-dose methotrexate (MTX) are known as MTX-associated LPD (MTX-LPD). More than half of the cases of MTX-LPD undergo spontaneous regression after the discontinuation of MTX, while approximately 33% of these cases relapse after a certain period. MTX-LPD is currently the most serious obstacle to RA treatment. Integrated analysis with genome-wide association analysis (conducted in previous research) and RNA transcriptome analysis was performed to comprehensively search for genes related to MTX-LPD pathophysiology. Our findings suggest that Gene A, which is associated with therapeutic effects, and Gene B, which is associated with MTX-LPD regression pathology, can be used to develop precision medicine. It is expected that the results of this project will lead to the development of genomic medicine.
Free Research Field	血液病理
Academic Significance and Societal Importance of the Research Achievements	MTX-LPDは、リウマチ（RA）治療薬である MTXの低容量投与中に発生するLPDで、時に MTX投与の中止にて腫瘍が退縮する“リバーシブルなリンパ腫”という興味深い病態を示す。本課題では先行のGWAS解析にてゲノムワイド水準を上回ったSNP情報からえられた候補遺伝子とRNAトランスクリプトーム解析の統合的解析を行う。これにより、MTX-LPDの病態のメカニズムの解明、それに伴うゲノム医療の実践、治療薬の開発等の社会貢献が期待できる。