Fig. 5: Treatment with BET-PROTAC ARV-771 depletes c-Myc, CDK4, TCF4, IRF4, and Bcl-xL expression and exerts synergistic lethal activity with ibrutinib in RT-DLBCL cells.

A RT-DLBCL cells were treated with the indicated concentrations of ARV-771 for 48 h. At the end of treatment, the % of To-Pro-3 iodide-positive, non-viable cells was determined by flow cytometry. Mean of three experiments ± SEM. B–D Comparison of selected, significantly altered (≥1.25 fold change up or down and p-value < 0.05 relative to untreated control), mRNA expression changes detected by RNA-Seq analysis (on biologic triplicates) in HPRT3, HPRT2, and HPRT1 cells following treatment with BET-PROTAC ARV-771 for 8 h. E HPRT3, HPRT2, and HPRT1 cells were treated with 1000 nM of OTX015 or 250 nM of ARV-771 for 24 h. Immunoblot analyses were conducted on the cell lysates. The expression levels GAPDH in the cell lysates served as the loading control. F RT-DLBCL cells were treated with ARV-771 (dose range: 20–250 nM) and/or ibrutinib (dose range: 2–10 µM) for 48 h. The % of non-viable cells was determined by flow cytometry. Combination index (CI) values were calculated with CompuSyn and boxplots were graphed with GraphPad V8. CI values <1.0 indicate a synergistic interaction of the two agents.