Anti-proliferative effects of new molecular-targeted drugs on Intraocular lymphoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K24024
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Karakawa Ayako 東京大学, 医学部附属病院, 届出研究員 (90844176)
• Project Period (FY): 2019-08-30 – 2023-03-31
• Keywords: 眼内悪性リンパ腫 / 分子標的治療 / 遺伝子変異

Outline of Final Research Achievements

We established the diagnostic method for Intraocular lymphoma (IOL) using Digital PCR. We detected disease specific genes, MYD88, CD79B, GENEX and GENEY, using this method. Recently, chemotherapy with Bruton-type tyrosine kinase (BTK) inhibition has attracted attention as the therapeutic approach of MYD88 mutant disease. In this study, we investigated the effect of GENEX inhibitor, GENEY inhibitor and the combination with BTK inhibitors on MWCL-1. The growth inhibitory effect was analyzed using WST-8 assay. All of the BTK inhibitors (ibrutinib, acalabrutinib), GENEX inhibitor, and GENEY inhibitor suppressed the proliferation of the MWCL-1 cell line in a concentration-dependent manner.

Free Research Field

眼内悪性リンパ腫

Academic Significance and Societal Importance of the Research Achievements

眼内悪性リンパ腫の検体量は微量で、疾患特異的遺伝子を見出すことは困難で更なる候補治療薬の検討は難しかった。申請者は、digital PCR解析を用い、新規変異遺伝子を含む4遺伝子(MYD88,CD79B,GENEX,GENEY)を見出し、治療候補薬を検討した。MYD88遺伝子変異を有する細胞株(MWCL-1)を用いて、全ての疾患特異的遺伝子阻害剤(第1及び第2世代BTK阻害剤、GENEX、GENEY阻害剤)は、MWCL-1の増殖を濃度依存的に抑制する傾向がみられ、各分子標的薬の増殖抑制効果が示された。生命予後不良な眼内悪性リンパ腫の疾患特異的治療薬の新たな開発に繋がる可能性がある研究である。