Figure 2.

Dynamics of gene mutations in the myelodysplastic syndromes to secondary acute myeloid leukemia progression axis. (A) Comprehensive landscape of mutational dynamics in the discovery and control cohorts. Genes are grouped by cellular functions and are represented in rows; each column represents a patient. Dynamics are represented by a color gradient: red/orange for newly acquired/increasing mutations, yellow for stable mutations, and blue/green colors for decreasing mutations. (B) Co-occurrence of cohesin complex and Ras signaling mutations in the discovery cohort. Circos plot of statistically significant associations between mutations detected in the discovery cohort, grouped by functional pathways. Graphs represent patients with mutations in the cohesin complex and Ras signaling, and the most frequently mutated genes in these pathways, STAG2 and NRAS, showing a statistically significant association (P=0.023 and P=0.002, respectively). (C) Incidence of this co-occurrence pattern in the discovery and validation cohorts. The table contains the number of patients with the combination of cohesin and Ras signaling mutations in the discovery and validation cohorts and an indication of whether they evolved to secondary acute myeloid leukemia (sAML). (D) Prognostic impact of the co-occurring mutations in the cohesin complex and Ras pathway. Kaplan-Meier curves for overall survival and sAML progression-free survival in patients bearing co-occurring cohesin and Ras pathway mutations in the entire validation cohort. VAF: variant allele frequency; LR: low-risk; HR: high-risk; NS: not significant; *P<0.05.