The Effect of Combined Bcr-Abl Inhibitor and ALDH Inhibitor on Chronic Myelogenous Leukemia

Abstract

【Introduction】Chronic myelogenous leukemia (CML) has become a disease with five-year-survival rate of more than 90% according to appearance of Bcr-Abl inhibitor. Stopping treatment with Bcr-Abl inhibitors leads to relapse in many patients. This is due to the fact that Bcr-Abl inhibitors are not effective against cancer stem cells, and suggests that a different drug is necessary to eradicate cancer stem cells. ALDH is overexpressed in cancer stem cells and promotes their survival. We have shown in past studies that Bcr-Abl inhibitors do not inhibit ALDH expression. In this study, we examine the effect of ALDH inhibitors on CML.

【Methods】We examined the effects of an ALDH inhibitor using K562 cells, which are CML cell line. We verified the effect of an ALDH inhibitor against CML using a WST-8 assay. We then measured ALDH protein expression using flow cytometry.

【Results】ALDH inhibitors reduced cell survival in a concentration-dependent manner, and when combined with a Bcr-Abl inhibitor, cell viability was synergistically decreased. ALDH protein expression was decreased in cells treated with ALDH inhibitor alone or Bcr-Abl inhibitor alone according to flow cytometry. In cells treated with ALDH inhibitor and Bcr-Abl inhibitor, ALDH protein expression was more strongly repressed.

【Conclusion】The results of this study suggest that ALDH inhibitor use might be effective in CML treatment.