As an alternative 2G-TKIs in patients who are resistant to a 2G-TKI without specific mutations, a third-generation TKI, ponatinib is suggested due to its higher efficacy in eradicating CML stem cells and overcoming TKI resistance by replacing threonine with isoleucine at the ATP-binding site, as well as targeting the VEGFR, KIT, SRC, FGFR, PDGFR, FLT3, and KIT pathways [167]. This evidence concerns the gene FLT3 and chronic myelogenous leukemia, BCR-ABL1 positive.