These inhibitors are unlikely to provide cure of the AML due to primary resistance from co-mutations in other pathways especially the NRAS/KRAS, and MAPK pathway effectors PTPN11, NF1, FLT3 and others [38] and secondary resistance from development of second-site IDH2 missense mutations or isoform switching [39, 40]. This evidence concerns the gene FLT3 and acute myeloid leukemia.