2023 Fiscal Year Final Research Report

Establishment of the platform for a drug discovery of multiple myeloma by targeting PBK-related signaling pathway

Research Project

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Project/Area Number	21K08426
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 54010:Hematology and medical oncology-related
Research Institution	Kinjo Gakuin University (2023) Aichi Medical University (2021-2022)
Principal Investigator	Ota Akinobu 金城学院大学, 生活環境学部, 教授 (30438048)
Co-Investigator(Kenkyū-buntansha)	武井則雄北海道大学, 医学研究院, 助教 (50523461) 花村一朗愛知医科大学, 医学部, 教授 (70440740) シバスンダランカルナン愛知医科大学, 医学部, 講師 (30557096)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	多発性骨髄腫 / 悪性化 / 治療標的分子 / 細胞生物学 / 薬剤スクリーニング
Outline of Final Research Achievements	Multiple myeloma (MM) is an incurable plasma cell hematological malignancy. This study is aimed to precisely elucidate the molecular pathology related to the malignant transformation of MM. We have identified malignant factors from the gene group induced by Interleukin-6, analyzed the gene functions, and attempted to identify new therapeutic agents. Here, we conducted drug screening, identified novel malignant factors located in the 1q genomic amplification region, and analyzed the properties of PBK knockout mice to verify the potential of PBK and related molecules as therapeutic targets. The results revealed that (1) PBK expression is related tothe sensitivity of immunomodulatory drug, (2) a novel malignant factor enhances DNA repair ability in MM cells, and (3) PBK knockout mice do not exhibit any major phenotypes. These results strongly suggest that inhibition of PBK may lead to the development of novel therapeutic agents that suppress the malignant transformation of MM.
Free Research Field	がんの分子生物学
Academic Significance and Societal Importance of the Research Achievements	多発性骨髄腫（Multiple myeloma、以下MM）は、形質細胞性の難治性血液悪性腫瘍である。現在の医療では、MMの再発や悪性化を完全に抑制することは難しく、MM悪性化の克服はMM患者の更なるQOL延伸に向けた喫緊の課題である。本研究は、遺伝子発現解析をもとにMMの悪性化に関わる分子機構の解析を試み、MMの新たな治療標的分子PBKに関する治療応用の可能性を検証したものであり、学術的・社会的意義は極めて高い。解析の結果、PBKの喪失は、マウスに顕著な表現型を示さない一方、一部のMM細胞に対する薬剤感受性に影響を及ぼすことから、PBKを標的とした分子標的薬開発は有望である可能性が示唆された。