Chronic myelogenous leukemia.

Chronic myelogenous leukemia involves clonal expansion of hematopoietic progenitor cells associated with the characteristic translocation between chromosomes 9 and 22, resulting in the generation of an aberrant bcr-abl protein with enhanced tyrosine kinase activity. The bcr-abl protein can induce cell proliferation, induce transformation of immature hematopoietic cells, and suppress apoptosis in vitro. Abnormalities of stromal cell and progenitor cell interaction may be central to the pathogenesis of the abnormal hematopoiesis in chronic myelogenous leukemia. Therapy with interferon alpha in chronic-phase chronic myelogenous leukemia can result in hematologic responses in up to 70% to 80% of patients and partial or complete cytogenetic responses in up to 50%; many studies show a significant overall survival advantage for patients treated with interferon. Allogeneic marrow transplantation can result in long-term survival for patients with chronic myelogenous leukemia, particularly younger patients undergoing transplantation early in the course of 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 expansion ex vivo of Ph- stem cells for reinfusion as part of a strategy for autologous marrow transplantation. Other areas of current investigation include in vitro assessment of the activity of antisense oligonucleotides and of the immunologic responses to chronic myelogenous leukemia cells.