Fig. 6

Mutation spectrum and clonal patterns of patients treated with crenolanib. a Graph depicts mutations identified by exome sequencing, gene panel and/or targeted sequencing. Each column displays a patient; each row denotes a specific gene. Recurrently mutated genes are color-coded for only present before crenolanib treatment, only present in after crenolanib treatment samples, persistence before and after crenolanib treatment, with no samples available before or after crenolanib treatment. b Graph depicts primary drug-resistant clone. In this case, FLT3 mutation clones co-occur with a TET2 mutation clone and the variant allele frequencies (VAFs) of the combined mutation persist during drug treatment. c The second pattern is the acquisition or expansion of additional mutations in the context of a FLT3 mutation. In this case, the original, dominant FLT3 tyrosine kinase domain (TKD) clone was inhibited by crenolanib after three cycle treatments. However, CEBPA mutation was acquired and expanded at the time of drug resistance in FLT3 TKD clone. d The third pattern is the acquisition of subclones independent of FLT3 mutation clones. In this case, FLT3 mutation clones were eliminated by crenolanib; however, a PTPN11 mutation clone emerged during crenolanib treatment. Of note, the clonal patterns shown do not include mutation information before crenolanib treatment. C: crenolanib treatment cycle number; Chemo: chemotherapy. The y-axis stands for VAF