For example, despite the clinical efficacy of the first-, second-, and third-generation BCR-ABL inhibitors, resistance occurs invariably and more than 50 distinct point mutations encoding single amino-acid substitutions in the kinase domain of the BCR-ABL1 gene have been detected in patients with imatinib-resistant CML [64,104]. The gene discussed is BCR; the disease is chronic myelogenous leukemia, BCR-ABL1 positive.