Berbamine overrides TKI-resistance to leukemia stem cells and T315I mutant–Bcr-Abl of CML. (A-D) Effect of berbamine (A-B) and IM (C-D) on the growth of IM-resistant K562 cells containing LSCs and IM-resistant T315I mutant Bcr-Abl cells (KCL-22M). Two pairs of CML cell lines: K562 cell and IM-resistant K562 cells (containing 2.5% LSCs), KCL-22 and IM-resistant KCL-22M (T315I mutant Bcr-Abl clone) were treated with berbamine or IM at various concentrations for 72 hours and cell viability were measured using MTT assay. IM-sensitive K562 and KCL-22 cells were used as controls. (E) Effect of BBM and IM on the growth of CD34⁺ and CD34⁻ leukemia cells. CML CD34⁺ stem cells and CD34⁻ leukemia cells were treated with BBM or IM at various concentrations. After 72 hours in culture, cell viability was measured using MTT assay and IC50 values were calculated. IM was used as control (*P < .01).