Journal
CYTOKINE & GROWTH FACTOR REVIEWS
Volume 18, Issue 5-6, Pages 459-471Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.cytogfr.2007.06.015
Keywords
interferon-alpha; biological agents; chronic myeloid leukemia; leukemic stem cell
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Biological agents have long been used in the treatment of cancer, and interferon-alpha was the first human cytokine to be widely studied in this setting. Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder for which interferon-alpha has demonstrated substantial activity. In the 1980s interferon-alpha became first-line therapy for patients with chronic-phase CML, not eligible for allogeneic stem cell transplantation. Following the discovery of the leukemic oncogene BCR/ABL and its causal association with CML, the potent BCR/ABL tyrosine kinase inhibitor imatinib mesylate was developed. Imatimb proved to be superior to interferon-alpha in all outcome measures, making imatinib the new standard of care for patients with CML. There is both clinical and laboratory evidence suggesting imatimb therapy alone is not curative in CML, whereas IFN has induced a low but reproducible curative effect in some patients. This unique activity may be the basis for the reincorporation of IFN into the management of CML. These observations may be best explained by imatinib's negligible activity against the leukemic stem cell (LSC) population. This review discusses the history of interferon-alpha in the treatment of CML, the evolution of molecularly targeted therapies, and some of the lessons we have learned from years of informative research in CML. It also explores the new challenge of managing minimal residual disease in the imatimb era, and addresses the promising role for LSC-directed therapies in the future treatment of CML. (c) 2007 Elsevier Ltd. All rights reserved.
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