However CML patients risk toxicity and drug-resistance, and despite second (Dasatinib, Nilotinib) and third (Ponatinib) generation TKIs, resistance does occur due to mutations or amplification of the BCR-ABL fusion gene, or to various Bcr/Abl-independent resistance mechanisms, such as mutations in genes encoding other tyrosine kinases (Src-kinase related LYN, KIT, MET) or deregulation of the expression of drug influx protein Oct-1 [62,80,81,82,83,84]. This evidence concerns the gene BCR and chronic myelogenous leukemia, BCR-ABL1 positive.