Inhibitors of BCR signaling differentially regulate expression of proapoptotic and antiapoptotic BCL2 family members. (A) Top panel, Induction of apoptosis after 96-hour exposure to DMSO, entospletinib (ENTO, 2 μM), ibrutinib (IBRU, 0.1 μM), copanlisib (COPA, 0.25 μM), or pictilisib (PICTI, 0.5 μM) shown as percentage of annexin V/PI-positive cells plus or minus SEM from at least 3 biological replicates. Bottom panel, Induction of PARP cleavage after 24-hour exposure to the drugs listed in the panel A description was assessed by immunoblotting, β-actin–loading control. One representative image of 3 independent replicates is shown. Vertical lines have been inserted to indicate repositioned gel lanes. (B) HRK, BCL-xL, BFL-1, or BIM transcript abundance after 24-hour exposure to DMSO, entospletinib (2 μM), ibrutinib (0.1 μM), copanlisib (0.25 μM), or pictilisib (0.5 μM) was determined with RT-qPCR relative to PPIA. Bars show the average of 3 technical replicates plus or minus SEM. The statistically significant differences between DMSO- and copanlisib-treated groups (q ≤ 0.05) are noted. (C) MCL-1 and BCL-2 protein abundance in DLBCL cells treated as in panel B was assessed by immunoblotting. β-actin–loading control. One representative image of 3 independent biological replicates is shown. Vertical lines have been inserted to indicate repositioned gel lanes.