Combination of eltanexor and venetoclax induces apoptosis and leads to loss of clonogenicity. (A) MV-4-11, MOLM-13, and NB4 cells were treated with twofold dilutions of eltanexor, venetoclax, or their combination for 72 hours. Contour plots of synergy scores were generated from a dose matrix of eltanexor and venetoclax using the ZIP model. The synergy scores were represented by pseudocoloring 2-dimensional (left) or 3-dimensional (right) contour plots over the dose matrix, giving rise to the overall synergy landscape. Red indicates synergy and green indicates antagonism for the various concentrations of combined eltanexor and venetoclax. Note different scale bars for ZIP synergy scores for the cell lines. Plots are representative of 3 independent experiments. (B) p53, BCL2, MCL1, and PARP and cleaved PARP (PARP/cPARP) protein expression was measured by immunoblot in MV-4-11, MOLM-13, and NB4 cells after 24-hour treatment with DMSO (D), eltanexor (E), venetoclax (V), or eltanexor-venetoclax combined (E/V). Actin was used as a loading control. Vertical lines indicate different exposures because of varying levels of endogenous protein levels between the cell lines. (C) Apoptosis was measured by annexin V (AnnV)/PI staining using flow cytometry after 24 hours of treatment. The percentages of early apoptotic (AnnV⁺; blue bar) and late apoptotic/dead (AnnV⁺/PI⁺; red bar) cells were measured. Statistical differences were calculated on the basis of the total number of AnnV⁺ cells for each treatment group. (D) Colony assays in MV-4-11, MOLM-13, and NB4 cells after 24 hours of drug treatment. The plot shows number of colonies per 500 cells plated. The data in panels C-D are presented as mean ± standard deviation (SD) from 3 independent experiments. *P < .05; **P < .01; ***P < .001; ****P < .0001.