Incidence and impact of SH2B3 mutations in JMML. (A) Frequencies of mutations identified by targeted or genomic sequencing in a cohort of 213 JMML cases. A case is considered positive for any mutation found at diagnosis or relapse. Red bars indicate canonical Ras-pathway genes that are thought to initiate JMML; blue bars represent secondary mutations. (B) Kaplan-Meier analysis of outcomes for JMML, comparing patients with single mutations to those with secondary mutations in SH2B3 (log rank P < .01). (C) WBCs, hemoglobin F levels, and age at diagnosis in groups assigned as in panel B (Wilcoxon P < .05 for WBC and P < .01 for hemoglobin F). MUT, mutated; WT, wild type.