(A) Using gene editing and transcriptional profiling in human MM cell lines, Durand et al defined a 13 gene signature to generate a measure of p53 activity. This p53 score could discriminate patient samples that had biallelic loss of TP53. (B-C) The authors then focused on the function of 1 gene in the p53 score, BAX, and demonstrated that BAX expression resulted in increased dependence of cells on MCL1 and MCL1 inhibitor (MCL1i) sensitivity. Loss of TP53 and subsequent lower BAX expression render cells less dependent on MCL1; therefore, they are less sensitive to MCL1i. Professional illustration by Patrick Lane, ScEYEnce Studios.