ARK5 in multiple myeloma with poor prognosis

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K17866
• 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: Nagoya City University
• Principal Investigator: Shiori Kinshita 名古屋市立大学, 医薬学総合研究院(医学), 助教 (70832062)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: ARK5 / 多発性骨髄腫

Outline of Final Research Achievements

We conducted this study to elucidate the contribution of ARK5 in the two points. (1) Acquisition of resistance to molecular target medicine (2) Extension to extramedullary lesion. Finally, we tried to search effective treatment for high grade multiple myeloma with ARK5 activation. We found ARK5 might associate to acquisition of resistance to immunomodulatory drug, lenalidomide. We further showed increase expression of ARK5 under anoxia and undernutrition might promote extramedullary extension of multiple myeloma. In mechanism of ARK5 inhibitor, we indicated the change of mTOR and caspase pathway.

Free Research Field

医学　血液内科　多発性骨髄腫

Academic Significance and Societal Importance of the Research Achievements

多発性骨髄腫においても、低酸素下低栄養下におけるARK5の発現増強を認めたこと、ARK５とEMTの関連において、E-cadherinとARK5により、OSが層別化されること、は学術的意義のある知見であった。今後、多発性骨髄腫におけるEMTとARK5の関連の研究をすすめることで、多発性骨髄腫の髄外進展の機序の解明につながると考える。また、ARK5阻害薬の治療応用については、まだ道のりは長いが、患者由来の骨髄腫細胞においても腫瘍増殖抑制効果がみられており、さらに研究をすすめる予定である。