Chronic Myelogenous Leukemia

Chronic myelogenous leukemia, BCR-ABL1+ (CML) is a myeloproliferative neoplasm characterized by a BCRABL fusion gene and almost always exhibits the characteristic cytogenetic finding t(9;22)(q34;q11). The protein product of BCR-ABL1 is a constitutively active tyrosine kinase whose function is intrinsic to CML pathogenesis. Patients present with leukocytosis and often splenomegaly and prominent marrow hypercellularity with marked myeloid hyperplasia and basophilia in most cases. Unlike acute leukemias, the neoplastic myeloid cells in CML exhibit a full spectrum of maturation at the early stages of disease, but if untreated CML inexorably progresses to an acute leukemia. The recent development BCR-ABL1 tyrosine-kinase inhibitors has profoundly changed the clinical course of patients with CML; most patients achieve long-term remissions if they are treated in the early part of the disease course. Monitoring of resistance to tyrosine-kinase inhibitors and assessment for disease progression are critical in current CML management. Therapeutic approaches, including targeted therapy, is discussed.