Treatment strategy with ALDH1A1 inhibitor to prevent relapse of chronic myeloid leukemia

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16044
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: The University of Tokushima
• Principal Investigator: YAGI Kenta 徳島大学, 病院, 特任助教 (10869085)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 慢性骨髄性白血病 / 分子標的治療薬 / ALDH

Outline of Final Research Achievements

The purpose of this study was to clarify the relationship between relapse and ALDH in chronic myelogenous leukemia (CML). In this study, we found that ALDH inhibitors enhance the antitumor effect of CML chemotherapy, using drugs with ALDH inhibition as their main effect. We also found that expression changes of ALDH may be different for each isozyme when ALDH inhibitors or CML drugs affect the expression of ALDH. Based on these results, we found that ALDH inhibition may be one of the effective factors that inhibit CML relapse. We also used database analysis to identify several factors other than drugs that may be candidates for influencing treatment continuation.

Free Research Field

臨床薬理

Academic Significance and Societal Importance of the Research Achievements

分子標的治療薬の登場によりCMLは長期生存が見込める疾患となった。しかし、現状では一生涯の薬物治療を余儀なくされており、若年患者においては長期投与による副作用や高額な薬剤費に悩まされている。そのため、CML幹細胞を根絶できる治療戦略を確立することには非常に社会的意義がある。本検討で得られた知見を元にALDHとCML幹細胞の生存の関連を明らかとすることで、CML幹細胞の根絶できる治療法の開発に貢献しうる可能性を見出した。