Evaluation of M-protein related ubiquitin enzyme as a new biomarker for Multiple Myeloma

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08983
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Himeji Dokkyo University
• Principal Investigator: Mariko Takenokuchi 姫路獨協大学, 薬学部, 准教授 (10379430)
• Co-Investigator(Kenkyū-buntansha): 宮本 和英 姫路獨協大学, 薬学部, 准教授 (10415317) ; 西郷 勝康 姫路獨協大学, 看護学部, 教授 (20304107) ; 谷口 泰造 甲南大学, フロンティアサイエンス学部, 特別招聘研究員 (70346253)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 多発性骨髄腫 / ユビキチンープロテアソーム系 / プロテアソーム阻害剤 / M蛋白

Outline of Final Research Achievements

Although the proteasome inhibitor bortezomib has been used worldwide as a treatment for multiple myeloma (MM), there are no biomarkers of treatment response to bortezomib in MM patients. The aim of this study was to investigate a new biomarker focused on M-protein and to apply it in clinical application. We initially could not detect M-protein-specific ubiquitinated enzymes due to their molecular polymorphism. Next, to compare ubiquitinated proteins between bortezomib-sensitive cell line and -resistant cell line, MS-based methods for identification of protein ubiquitination sites was utilized. We found 31 ubiquitinated proteins with a significant difference, out of which Histone H4 was markedly decreased. Bortezomib significantly increased ubiquitinated Histone H4 in MM cell lines. We focus on Histone H4 and are studying the possibility of a new biomarker for MM patients.

Free Research Field

検査血液学

Academic Significance and Societal Importance of the Research Achievements

多発性骨髄腫の治療成績は、新薬を含む9剤の承認により劇的に改善している反面、各薬剤の最大効果を引き出すために最適な治療レジメンを患者毎に適宜選択する必要がある。本研究は、第一選択薬であるプロテアソーム阻害剤ボルテゾミブの治療効果を予測するバイオマーカーを同定する研究であり、今回Histone H4がマーカーとなる可能性を見出した。今後、マーカーとしての有用性を示すことにより治療成績の向上、患者の身体的・経済的負担軽減に貢献できると考える。