170 - CHRONIC Myeloid Leukemia

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative disorder marked by the increased proliferation of a granulocytic cell line that retains the ability to differentiate. As many as 95% of patients with CML have the Philadelphia (Ph) chromosome caused by the reciprocal translocation of the long arms of chromosome 22 at the breakpoint cluster region (BCR) gene and chromosome 9 at the Abelson leukemia virus (ABL) gene (t[9;22]). As a result of this translocation, a BCR-ABL fusion gene is created that generates a chimeric protein with constitutively active tyrosine kinase activity. Tyrosine kinase inhibitor therapy has revolutionized the treatment of CML, giving patients with chronic phase disease a near-normal age-adjusted lifespan. For patients with chronic phase CML, the “first-generation” tyrosine kinase inhibitor imatinib gives a complete cytogenetic remission in roughly 60 to 70% of cases, a major molecular response (a three-log reduction of peripheral blood BCR-ABL mRNA) in 50 to 60% of cases, with overall survival rates of more than 90%. The “second-generation” tyrosine kinase inhibitors (e.g., dasatinib, nilotinib, and bosutinib) are more potent than imatinib and thus give higher short-term response rates and less progression to advanced phases of disease, although without a clear advantage in overall survival rates. Because of the success of tyrosine kinase inhibitors, CML will become a more prevalent oncologic diagnosis in the future, despite its relatively low incidence. CML is thus becoming an increasing part of most oncology practices, and an understanding of the pathobiology, monitoring, and treatment is important to optimize the management of CML patients.