Combination of simvastatin and imatinib sensitizes the CD34+ cells in K562 to cell death

Chronic myeloid leukemia (CML) is a hematological malignancy, 95% of which is due to translocation between chromosomes 9 and 22 and the resulting bcr-abl fusion protein. Imatinib specifically binds to the bcr-abl and inhibits cancer cells. However, a subpopulation of the CML cells named leukemia stem cells are resistant to the imatinib therapy, leading to the relapse. In this study, we identified a subpopulation of CD34+ cells in K562 were much more resistant to imatinib than the bulk cells. Simvastatin single also had little pro-apoptotic effect on the CD34+ cells. In contrast, combination of simvastatin and imatinib induced a significant cell death in the subpopulation, which is dependent on the induced ROS by simvastatin as the effect was blocked by ROS scavenger N-acetyl-l-cysteine (NAC). Our data here point out that combination of simvastatin and imatinib could be a therapeutic option for the resistant CML.