Figure 1. Random mutagenesis and in vitro drug-resistant screening reveal lack of genetic resistance against fedratinib.

(a) Frequency of resistance of BaF3 cells transformed with randomly mutagenized JAK2-V617F. For each experiment, 1.0 × 10⁷ BaF3 cells were transduced with randomly mutagenized JAK2-V617F virus. After 16 to 20 hours, cells were exposed to different concentrations of drug inhibitors, for two weeks. The number of clones obtained per 5 × 10⁶ cells from two independent experiments was averaged and plotted. (b) Frequency of resistant mutations from the FERM domain. (c) Frequency of resistant mutations from the SH2 and pseudokinase (JH2) domains. (d) Frequency of resistant mutations from the kinase-linker and kinase (JH1) domains.