AZD4785-dependent modulation of transcriptome of MM cells. (A) Normalized expression levels of KRAS transcript from clariom D profiling in MM.1S, MKS20, OP12, and U266 cell lines after 48 hours of AZD4785 exposure (3 μM), as compared with control (ctrl; q value 0 from SAM analysis); percentage of ctrl of AZD4785-treated vs untreated is shown. (B) Plot of the 20 most significant gene ontology biological process terms enriched in MM1S, KMS20, and U266 differentially expressed (DE) protein coding gene lists. (C) Heatmaps of DE transcripts in AZD4785-treated (3 μM; 48 hours) vs ctrl replicates in MM1S, KMS20, and U266 cell lines by SAM analysis (q = 0; absolute FC value > 2), respectively. Blue-red color scale was used to set rows with mean of 0 and standard deviation 1 of 1. Of note, OPM2 cells only presented with DE KRAS level; no other DE transcripts were observed. (D) MM.1S, KMS20, OPM2, and U266 cells were exposed to AZD4785 (0-3 μM) for 48 hours and subjected to wide transcriptome profiling, showing significant inhibition of KRAS-related gene sets in KRAS-mutated cells, as assessed by gene set enrichment analysis. Normalized enrichment score (NES) was generated by comparing AZD4785-treated vs untreated cells. NES, nominal P value, and false discovery rate (FDR) q value are reported for each plot. *P < .001. IFN-γ, interferon γ; n.s., not significant.