Chronic myeloid leukemia: Pathophysiology and therapeutics

Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative disorder -characterized by a translocation between the long arms of chromosomes 9 and 22. Often referred to as the Philadelphia (Ph) chromosome, this genetic rearrangement results in an oncogenic tyrosine kinase, Bcr-Abl. The disease may smolder for years before terminating in a blast crisis. Once curable, mostly with bone marrow transplantation and only seldom with interferon alpha-based therapy, its management has been radically changed with the introduction of imatinib mesylate, an orally available Abl kinase inhibitor, in 1998. More common in adults, only an estimated 50 pediatric cases occur annually in North America. The treatment of CML will remain in flux as second-generation Bcr-Abl kinase inhibitors are studied clinically. Because of its rarity in pediatrics, clinical insights must come from -experience with adult CML. CML serves as the paradigm of how molecular understanding of a cancer's pathophysiology can produce a revolutionary form of -targeted therapy, providing hope for those pediatric cancers with a well-defined genetic lesion.