Mefloquine selectively targets BP-CML CD34+ cells, with enhanced effects when combined with TKIs. (A) Mefloquine reduces cell viability in CML and CML (T315I) CD34+ cells, with enhanced effects when combined with dasatinib (100 nM) and ponatinib (5 nM) respectively. Less reduction in cell viability is observed with cord blood (CB) CD34+ cells. Cells were treated with drugs for 3 days prior to apoptosis analysis. (B) Mefloquine inhibits colony formation in CML and CML (T315I) CD34+ cells, with greater inhibition when combined with dasatinib (50 nM) and ponatinib (5 nM) respectively. Less inhibition is observed with CB CD34+ cells. Mefloquine inhibits the serial replating capacity in CML and CML (T315I) CD34+ cells, with greater inhibition when combined with dasatinib (50 nM) and ponatinib (5 nM) respectively for both the first (C) and second (D) replating. Less inhibition is observed with CB CD34+ cells. CML samples harbor other BCR-ABL1 mutations but not T315I. CML (T315I) samples harbor T315I mutation. Drugs were added simultaneously for combination studies. Data are representative of at least three independent experiments. All error bars as shown are standard deviation. *, P ≪ .05, compared to control; #, P ≪ .05, compared to TKI.