Specific targeting of MDR1 sensitizes AML cells to SM-induced killing. (A) HoxA9/Meis1 AML cells were treated with Bir (125, 250, and 500 nM), with or without Tari or the ABC transporter inhibitor Fum-C (inhibits BCRP/ABCG2) or reversan (Rev; inhibits MRP1/ABCC1 and MDR1; 100 and 1000 nM), for 24 hours (n = 3). P values were obtained by comparison of Bir alone and in combination with MDR1 or other ABC transporter inhibitors. (B) Whole-cell lysates from KG1 parental, controls 7A and 4B, and MDR1^−/− 2.48 and 3.30 cell pools were probed with the indicated antibodies. (C) Rho-123–retention assay in KG1 control 4B and MDR1^−/− 2.48 and 3.30 AML cells pretreated with Rho-123 (250 nM), with or without Tari (1 μM).Rho-123 fluorescence was determined by flow cytometry. KG1 controls 7A and 4B (n = 4-6) (D), MDR1^−/− 2.48 (n = 2-3; error bars, SD) (E), and MDR1^−/− 3.30 (n = 2-3; error bars, SD) (F) AML cells were treated with Bir (0.08, 0.4, and 2 μM), with or without Tari or Zosu (0.5 and 1 μM), for 48 hours. P values were obtained by comparison of Bir alone (blue) and in combination with Tari (red) or Zosu (green) at the indicated concentrations. Underscored P values correspond to 1 μM MDR1i. (G) KG1 control 4B and MDR1^−/− 3.30 and 2.48 AML cells were treated with Bir (500 nM), with or without Tari (1 μM), for 10 and 20 minutes. Whole-cell lysates from these samples were probed with the indicated antibodies. Data are the mean ± SEM throughout, unless otherwise stated. Cell survival was measured by flow cytometry analysis of PI exclusion. Actin was used as the loading control. M# indicates individual membranes. *P < .05; **P < .01; ***P < .001; ****P < .0001.