Upregulated immune response pathways are present in trametinib-sensitive samples. (A) Volcano plot displaying trametinib sensitivity according to gene from the BeatAML database with sensitive samples highlighted in red. (B) Differential CD274 expression for samples from the BeatAML database with 25% highest and 25% lowest AUC values. (C) A functional interaction (FI) network constructed for genes with correlations between transcript expression and trametinib response (AUC) >0.3 or <−0.3 and an FDR <0.01. Genes are displayed as nodes and FIs between genes as edges: solid lines are for annotated FIs, dashed lines for predicted FIs, -> for activation or catalysis, and -| for inhibition. This FI network significantly enriches many pathways, 3 of which are highlighted: Toll-like receptor pathways (FDR = 1.4E-13), cytokine-cytokine receptor interaction (FDR = 4.4E-4), and NOD-like receptor signaling pathway (FDR = 4.4E-4). (D) GSEA analysis uncovers pathways in immune systems that are significantly upregulated in trametinib-sensitive AML samples. Immune system pathways are organized into 3 categories in Reactome (https://reactome.org/PathwayBrowser/#/R-HSA-168256): Adaptive Immune Systems, Innate Immune System, and Cytokine Signaling in Immune System. (E) Distribution of correlations of gene expression and trametinib response for genes annotated in Toll-like receptor cascades (red lines) in the background for all genes, indicating the significantly skewed distribution of pathway genes on the negative correlation side. (B) Displaying 2-sided, 2-sample Student t test with unequal variances; statistically significant results displayed as: **P < .01.