ABBV-319 inhibits prosurvival signaling and induces apoptotic cell death in DLBCL. (A) The percentage viability relative to the untreated control after treatment of SU-DHL-6 cells with Af. isotype mAb and Af. CD19 mAb. Mean ± SEM is displayed. (B) SU-DHL-6 cells were pretreated with 100 nM Af. Isotype mAb or Af. CD19 mAb for an hour and then stimulated with 1 μg/ml anti-immunoglobulin M (anti-IgM) for the indicated time. Cell lysates were resolved on sodium dodecyl sulfate–polyacrylamide gel electrophoresis and immunoblot analysis for phospho-AKT (Ser473) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) are displayed. GAPDH is used as a loading control. (C) Volcano plot showing the fold change and P value from the meta-analysis of DEGs between 24-hour ABBV-319 treatment and vehicle control in ABBV-319-sensitive cell lines. Each dot represents a DEG and the genes involved in apoptosis are highlighted in red. (D-F) Immunoblot analysis of BIM, caspase 3, PARP, and GAPDH after treating Farage (D), SU-DHL-6 (E), and OCI-LY19 (F) with 10 nM GRM payload and 100 nM ABBV-319 for the indicated time. Arrows show the cleaved product of caspase 3 and PARP. (G-I) Cell cycle analysis of Farage (G), SU-DHL-6 (H), and OCI-LY19 (I) after treatment with 10 nM GRM and 100 nM ABBV-319 for the indicated time. The percentage of cells from sub-G1, G0-G1, S, and G2-M phases of the cell cycle are displayed.