Dexamethasone synergizes with MCL-1 inhibition to induce apoptosis of HMCLs. (A) Overview of the drugs that were implemented in the in vitro lethality screen, including their abbreviations and representing drug class. (B) Matrices showing the combined effect of 2 drugs in inducing specific apoptosis of the HMCLs MM1.s, OPM-2, and L363. Observed (OBS) specific apoptosis is compared with expected (EXP) specific apoptosis and represented by a color scale in which blue indicates an antagonistic effect, white an exact additive response, and red a synergistic effect. Drug abbreviations as represented in panel A. Drug concentrations are described in supplemental Table 1. Viability is analyzed after 48 hours of drug exposure. (C) Data as shown in panel B, ranked by the average effect of the drug combinations on OBS-EXP specific apoptosis of the 3 HMCLs. Mean values are indicated by solid black lines. The dashed line indicates an exact additive effect. (D) Heatmaps showing specific apoptosis of indicated HMCLs induced by serial dilution of dexamethasone (DEX) and MCL-1i, individual or combined. Viability was analyzed after 48 hours of drug exposure; values represent the mean of 3 individual experiments. (E) Plots comparing EXP vs OBS specific apoptosis induced by DEX and MCL-1i combinations. Per HMCL, the drug combination that resulted in the highest average OBS-EXP ratio was selected from the data obtained in panel D. The 3 connected data points show the data obtained from 3 individual experiments. Statistical analysis was performed by using paired Student t tests. (F) Representative western blot showing MCL-1, BCL-2, and BCL-XL protein expression of indicated HMCLs after 24 hours of exposure to DEX 1 μM or negative control. α-tubulin was used as a loading control. HDAC, histone deacetylase.