Pevonedistat induces a decrease in the cell viability of MCL cell lines or primary tumor cells isolated from lymphoma patients. (A) In vitro exposure of MCL cell lines to pevonedistat resulted in dose- and time-dependent (48-hour time point shown) cell death in cytarabine-sensitive cells (Granta, HBL-2, Mino, Z-138, Jeko-1, Rec-1) and cytarabine-resistant cells (HBL-2 AraCR, Mino AraCR, Jeko-1 AraCR, Rec-1 AraCR). Cytarabine-sensitive and -resistant cells were exposed to escalating doses of pevonedistat (0-4000 nM) for 24, 48, and 72 hours. Cell death was determined by Cell Titer-Glo luminescence assay. (B) Pevonedistat IC₅₀ levels at 48 hours. (C) Ex vivo exposure of primary lymphoma cells derived from patients with MCL to pevonedistat resulted in varying degrees of cell death. Pevonedistat or vehicle control was used at 500 nM in MCL cells. Cell death was determined by Cell Titer-Glo luminescence assay, to detect adenosine triphosphate generation after 48 hours. All experiments were repeated 3 separate times and were reported as the median with standard deviation error bars. (D) Clinical and pathological characteristics of the patient from which primary tumor cells were obtained. *P < .05.