Dexamethasone (DEX) reduces mTORC1 signaling and mTORC1 inhibitor rapamycin synergizes with MCL-1i. (A) Representative western blot showing total 4E-BP1 and 4E-BP1 phosphorylation on threonine residue 37/46 (p4E-BP1 T37/46), and total P70S6K and P70S6K phosphorylation on threonine residue 389 (pP70S6K T389) in indicated HMCLs after 4 hours of exposure to 1 μM DEX or negative control. α-tubulin was used as a loading control. Quantification findings are given in supplemental Figure 7. (B) Representative western blot showing total S6 and S6 phosphorylation on serine residues 235/236 (pS6 S235/6) and 240/244 (pS6 S240/4) in indicated HMCLs after 4 hours of exposure to 1 μM DEX or negative control. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as a loading control. (C) Heatmaps showing specific apoptosis of indicated HMCLs induced by serial dilution of rapamycin (RAPA) and MCL-1i, individual or combined. Viability was analyzed after 48 hours of drug exposure; values show the mean of 3 individual experiments. (D) Plots comparing expected (EXP) specific apoptosis vs observed (OBS) specific apoptosis induced by RAPA 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 C. The 3 connected data points show the data obtained from 3 individual experiments. Statistical analysis was performed by using paired Student t tests.