Combination birinapant/tariquidar therapy kills human primary leukemias. (A) MDR1 activity was determined in primary human CD34⁺ HSPCs through a Rho-123–retention assay. Cells were pretreated with Rho-123 (250 nM), with or without Tari (1 μM), and fluorescence was determined by flow cytometry. (B) Human CD34⁺ HSPCs were treated with Bir or VP16 (0.4, 2, and 10 μM), with or without Tari (1 μM), for 24 to 48 hours (n = 2-7 independent samples, error bars SD). (C-L) MDR1 activity was determined through a Rho-123–retention assay and cell death analysis of samples from patients 1 to 10. Cells from the patients were treated with Bir (0.016, 0.08, 0.4, 2, and 10 μM), with or without Tari (1 μM) and with or without TNF (25 ng/mL), for 24 to 48 hours (1 independent experiment for each sample). Cell survival was measured by flow cytometry analysis of AxV exclusion and is represented relative to control.