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. 2017 Dec 11;128(1):427–445. doi: 10.1172/JCI93801

Figure 7. Hierarchical model of drug response phenotypes in CLL.

Figure 7

(A) We derived a decision tree model that classifies CLL patients into 4 drug-response-based groups. First, we asked if ibrutinib caused strong viability effects (BTK group n = 50/184), second, whether the remaining patient samples responded to everolimus (mTOR group n = 26/184) and third, whether they responded to selumetinib (n = 23/184). The remaining patients were classified as weak responders (n = 85/184) (Supplemental Figure 10). (B) Summary of cosensitivities for the 4 groups. We compared drug responses of each group to all samples from the remaining groups (average of the 2 lowest concentrations) using Student’s t test. Significant differences (FDR = 5%) with a mean effect size greater than 5% are shown. The heatmap visualizes mean viabilities, row-centered and scaled to zero mean and unit standard deviation. (C) Exemplary plots of individual sample data for 4 of the drugs shown in panel B. The BH3 mimetic navitoclax and the CK2 inhibitor silmitasertib had stronger viability effects in the mTOR group. AZD7762 and idelalisib had stronger viability effects in the BTK group.