TP53-related cancer pathways and expression of actionable immune checkpoints in patients with TP53-mutated AML (SAL and Bologna cohorts). (A) TP53 mutations were categorized as missense or no missense (frameshift, splice site and nonsense) using the IARC TP53 database (http://p53.iarc.fr/) and based on prior knowledge.^30,31  (B) Principal-component (PC) analysis of 770 immune genes (IO 360 panel) in patients with TP53-mutated (n = 42) and TP53WT AML (n = 22). Points are colored by TP53 mutational status (mutated, red; WT, blue). ClustVis was used for data analysis and visualization. (C) Heatmap of immune-cell-type–specific and biological activity scores in patients with TP53-mutated and TP53-WT AML (unsupervised hierarchical clustering; Euclidean distance; complete linkage). The number of TP53-mutated cases in each immune cluster (high, intermediate, and low) is indicated. ClustVis, an online tool for clustering of multivariate data, was used for data analysis and visualization. (D) Heatmap of cancer pathway scores in patients with TP53-mutated and TP53-WT AML (unsupervised hierarchical clustering; Euclidean distance; complete linkage). (E) Cancer pathway scores in patients with TP53-mutated and TP53-WT AML. Bars denote median values. Data were compared using the Kruskal-Wallis test for unpaired determinations. (F) Box plots summarizing the expression of negative immune checkpoints and immune genes related to T-cell infiltration, regulatory T cells, and cytolytic activity in patients with TP53-mutated and TP53-WT AML. Bars denote median values. Data were compared using the Mann-Whitney U test for unpaired determinations. NA, not available; PI3K, phosphatidylinositol 3-kinase.