Figure 4. Combined targeting of MCL1 and BCL2 is highly effective against DLBCL in vivo and in vitro.

(a) IC₅₀s (mean of quadruplicates ± SEM) were calculated with non-linear curve-fit regression after exposure of 23 DLBCL cell lines to serially diluted ABT-199 for 24 hours. Dinaciclib results shown for comparison. (b) Viability curves and apoptotic induction of selected lines after 24 hours’ ABT-199 exposure. Cells were seeded at equal density and exposed to serially diluted ABT-199 for cell viability assay (mean of quadruplicates ± SEM), or exposed as indicated to 1:1000 DMSO (0) or ABT-199 for apoptosis assay (mean ± SEM of triplicates). (c) Western blot of SU-DHL-4 cells after incubation for the indicated times with 1:1000 DMSO (−) or 1 μM ABT-199. Drug-treated band intensities were quantified relative to the corresponding DMSO bands, following normalization to tubulin loading controls. (d) Viability was assessed in the indicated lines following 24 hours’ exposure to 250 nM dinaciclib, ABT-199, or the combination (mean of quadruplicates ± SEM); CompuSyn CI vs. Fa plots for dinaciclib + ABT-199 in the six lines. (e) Fold change in percentage of GFP+ cells in U2932 cells infected with BCL2, MCL1, or vector after recovery from 1:1000 DMSO (0), ABT-199, or dinaciclib+ABT-199 combination at the indicated concentrations for 24 hours. (f) Viability at 250 nM and CI vs. Fa for U2932 following 24 hours exposure to ABT-199, additional drugs with activity against CDK9, or the combinations. Mean of quadruplicates ± SEM. (g) U2932 cells were xenografted to SCID mice and treated with IP vehicle/PO vehicle (control group, n=5), IP dinaciclib/PO vehicle (dinaciclib group, n=5), IP vehicle/PO ABT-199 (ABT-199 group, n=5), or IP dinaciclib/PO ABT-199 (combination group, n=5).