Pevonedistat induces apoptosis in MCL cell lines. (A) In vitro exposure of MCL cell lines to pevonedistat for 48 hours altered the balance of proapoptotic (Bak) and antiapoptotic (Bcl-xL and Mcl-1) Bcl-2 family members, leading to PARP cleavage. (B) Induction of apoptosis after pevonedistat was further tested by flow cytometry studies using annexin-V (AnnV)/PI staining at 48 hours. (C) Inhibition of caspase activation partially rescued MCL cell lines to the apoptotic effects of pevonedistat. Cytarabine-sensitive and -resistant cells were exposed in vitro to pevonedistat (0-4000 nM) with or without a pan-caspase inhibitor (Q-VD-OPh, 5 μM); cell viability was determined with Cell Titer-Glo luminescent assay after 48 hours. CTRL, control. *P < .05.