Fig. 1

Loss-of-function screenings converge on KDM1A/LSD1 as synthetic lethal target to the proteasome inhibitor carfilzomib. A Schematic representation of the experimental strategy used in this study, showing the workflow of the loss-of-function screening to identify synthetic lethal targets for carfilzomib. SL, synthetic lethal. B Venn diagram of the top target hits found with shRNA and drug library screening indicating that KDM1A/LSD1 is a common hit from both screens. C Analysis of the MMRF CoMMpass dataset IA18 showed a significant correlation between LSD1 expression (RNAseq, TPM) and overall survival in 128 MM patients (P = 0.001). Sub-populations with low (blue line) or high (red line) LSD1 expression were defined using one standard deviation from the mean expression. D Box plots of gene expression levels in 287 MM cases that completed a regimen compared to 69 MM patients who experienced disease progression/relapse after bortezomib treatment (CoMMpass dataset). Differential expression was tested by the Wilcoxon rank-sum test with continuity correction (P = 0.0001018)