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Key Points• Myeloma cells are highly sensitive to PRIMA-1 Met , independent of p53.• PRIMA-1Met induces myeloma cell death by impairing GSH/ROS balance.The aim of this study was to assess the efficiency of p53 reactivation and induction of massive apoptosis (PRIMA-1

Multiple myeloma is a plasma cell malignancy that is heterogeneous with respect to its causative molecular abnormalities and the treatment response of patients. The Bcl-2 protein family is critical for myeloma cell survival. ABT-737 is a cellpermeant compound that binds to Bcl-2 and Bcl-x L but not to Mcl-1. Using a myeloma cell line collection (n ‫؍‬ 25) representative of different molecular translocations, we showed that ABT-737 effectively kills a subset of cell lines (n ‫؍‬ 6), with a median lethal dose ranging from 7 ؎ 0.4nM to 150 ؎ 7.5nM. Of interest, all sensitive cell lines harbored a t (11;14). We demonstrated that ABT-737-sensitive and ABT-737-resistant cell lines could be differentiated by the BCL2/MCL1 expression ratio. A screen of a public expression database of myeloma patients indicates that the BCL2/MCL1 ratio of t(11;14) and hyperdiploid patients was significantly higher than in all other groups (P < .