Biology and treatment of chronic myelogenous leukemia

Chronic myelogenous leukemia (CML) involves the clonal expansion of hemopoietic progenitor cells associated with a characteristic translocation between chromosomes 9 and 22, resulting in the generation of an aberrant bcr-abl protein with enhanced tyrosine kinase activity. Although the precise molecular events leading to malignant expansion of the myeloid cell line are as yet undetermined, bcr-abl can induce cell proliferation, transformation of immature hemopoietic cells, and suppression of apoptosis in vitro. Abnormalities of stromal/progenitor cell interaction may be central to the pathogenesis of the abnormal hemopoiesis in CML. In chronic-phase CML, therapy with interferon-alfa (Intron A, Roferon-A) produces hematologic responses in up to 70% to 80% of patients and partial or complete cytogenetic responses in up to 50%, with many studies showing a significant overall survival advantage for responding patients. Allogeneic marrow transplantation can result in long-term survival and cure in patients with CML, particularly younger patients transplanted early in the course of the disease, and unrelated-donor or autologous marrow transplantation may be an option for patients without a matched sibling donor. Future therapy will likely involve selection and ex vivo expansion of nonleukemic stem cells for reinfusion as part of a strategy for autologous marrow transplantation.