Chronic myelogenous leukemia: update on biology and treatment

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder that follows a characteristic clinical course in which a chronic phase of variable duration precedes an accelerated, and ultimately blastic, phase, which is generally fatal. This disorder results from a clonal expansion of transformed hematopoietic progenitor cells and includes myeloid, monocytic, erythroid, megakaryocytic, and lymphoid lineages. At the molecular level, CML is characterized by the bcr-abl fusion gene, which results from the reciprocal translocation t(9;22)(q34;q11), creating the Philadelphia (Ph) chromosome. Chronic myelogenous leukemia was the first human disease for which a specific karyotype abnormality was demonstrated and could be linked to pathogenetic events of leukemogenesis. The outlook for patients with CML has changed dramatically over the last decade. The median survival time of patients has doubled to 5 to 7 years, with up to 50% of patients alive at 5 years. This development is due to refinements in allogeneic stem-cell transplantation and growing expertise in the use of interferon-alfa (Intron A, Roferon-A), a biological agent that has been shown to suppress the leukemic clone and to prolong survival in patients with CML. This review provides a concise update of the biology of CML, as well as current therapeutic options and management strategies.