Clinicopathologic features and genomic landscape of distinct RAS pathway genes in CMML. (A) Frequency of detected mutations at the time of diagnosis in patients with RASp mutant (RAS^MT) or wildtype (RAS^WT) CMML among the cohort of 814 patients. Statistical differences of median positive are shown (∗P < .05; ∗∗P < .01; ∗∗∗P < .001). (B) Frequency of detected mutations at the time of diagnosis in patients with RAS^MT (n = 342) compared with RAS^WT, considering only those in whom all RAS genes were sequenced (n = 196). Statistical differences of median positive are shown (∗P < .05; ∗∗P < .01; ∗∗∗P < .001). (C) Heat map representing mutual exclusivity (blue) or co-occurrence (red) between RAS pathway gene mutations and other somatic mutations, or recurrent cytogenetic abnormalities. The color gradient is based on OR of association. Asterisks represent statistically significant associations (P < .05). (D-E) Bar chart representing frequencies of clonal dominance of RASp mutations among all patients with RAS^MT CMML (D), or RAS^MT MD-CMML or MP-CMML (E), in which 2 or more somatic mutations were present. Clonal relationships were tested using Pearson goodness-of-fit tests, with clonal heterogeneity being defined in cases with goodness-of-fit P values < .05, suggesting significant variability of VAF distributions reflecting the presence of several clones. CK, complex karyotype.