Evolutionary dynamics of the major clones during ibrutinib (ibr) relapse. Clonal trends in selected patients with CLL (supplemental Figure 2 provides details for additional patients). (A-D) Detailed trends for 2 patients with RT (A-B) and 2 without RT (C-D). Samples being analyzed are shown at the top of the plots. Time on the x-axis is partially scaled, consistent with Figure 1. Clonal frequencies are shown on the left y-axis, and absolute lymphocyte count (ALC) values are shown on the right y-axis (gray shaded curves). Mutations that clustered in the same trends are shown in the same colors (green, TP53 clusters; purple, BTK clusters; orange, SF3B1 clusters; and Blue, other clusters). The clonal trends of the copy-number changes are shown below each plot using the same color scheme. (E) Semiquantitative heatmap summarizing clonal trends for all 9 patients; x-axis for each box shows lapse of time. *Minor clones present but not depicted. Rel, relapse; Resp, response.