MM-mutant KRAS and NRAS are associated with differential RAS expression and are “addicted” to the mutated RAS isoform. (A) Boxplots of KRAS and NRAS expression in tumor samples from newly diagnosed MM patients in CoMMpass. The distributions are stratified by RAS mutation status and VAF to evaluate their effects on gene expression. P values from Welch’s 2-tailed t tests are reported for relevant comparisons. (B) Scatterplot of the gene dependency scores from DepMap between NRAS-mutated and KRAS-mutated MM cell lines from RNA interference (18Q2 release) or CRISPR deletion (Avana 18Q2) functional screens. Comparing between the two data sets, the related RAS gene shows consistent essentiality, but not other genes. Dashed lines represent cutoffs (Δ) for differential gene dependency between the RAS-mutated lines. (C) Similar to panel B, comparing WT RAS and RAS-mutated myeloma cell lines.