Timing of NOTCH1 mutations and relationship with TP53 disruption in high-risk CLL. (A) NOTCH1 mutations and TP53 disruption in fludarabine-refractory CLL. In the heatmap, rows correspond to the NOTCH1 and TP53 genes, and columns represent individual patients color-coded based on the gene status (white, wild type; red, mutations of NOTCH1 and disruption of TP53). (B) NOTCH1 mutations and TP53 disruption in sequential CLL/RS samples. In the heatmap, rows correspond to the NOTCH1 and TP53 genes. Columns represent individual patients color-coded based on the gene status (white, wild type; pink, mutations of NOTCH1 and disruption of TP53 in the CLL phase; red, mutations of NOTCH1 and disruption of TP53 at RS transformation).