Although imatinib inhibits different kinases in various diseases (BCR-ABL in CML, KIT or PDGFR-alpha in gastrointestinal stromal tumors [GISTs], and PDGFR-alpha in hypereosinophilic syndrome [HES]) (reviewed in [14]), some tumors that become refractory to treatment with imatinib appear to have analogous secondary mutations in the kinase-coding domain of the genes encoding these three enzymes. This evidence concerns the gene PDGFRA and chronic myelogenous leukemia, BCR-ABL1 positive.