The prognosis of patients with Ph+ ALL remains poor and is limited by the development of secondary resistance to ABL-directed tyrosine kinase inhibitors (TKI), caused predominantly by BCR-ABL tyrosine kinase domain (TKD) mutations that prevent the TKI-induced inhibition of BCR-ABL activity [8,10–12]. The gene discussed is BCR; the disease is acute lymphoblastic leukemia.