Effect of inhibitors of SL metabolism on viability in HL-60 wt and chemotherapy-resistant counterparts. A: Cell viability assays. Cells (50,000/well, black-walled 96 well plates) were exposed to the GCS (PDMP, eliglustat), AC (DM102, SACLAC), and SPHK1 (SK1-i, FTY720) inhibitors at the concentrations shown for 72 h in media containing 5% FBS. Viability was measured by PI staining as detailed in Materials and Methods. B: Effect of SK1-i on apoptosis in HL-60 wt, HL-60/dnr, and HL-60/Ara-C cells. Cells were treated with SK1-i (10 μM) for 48 h in dnr- and Ara-C-free media and analyzed by flow cytometry using Annexin-V FITC/PI staining. Early-apoptosis populations are represented by FITC+/PI−. Late apoptosis is represented by FITC+/PI+. Data are the mean ± SEM (n = 6) for each experimental point. **,***Statistical significance versus untreated control; ##,###statistical significance versus wt cells treated with SK1-i. Experiments were conducted in dnr- and Ara-C-free media.