Targeted treatment of chronic myeloid leukemia: role of imatinib

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by clonal expansion of pleuripotent hematopoetic stem cells. The incidence of CML is 1 to 2 cases per 100,000 people per year; in the Western Hemisphere, CML accounts for 15% of leukemias in adults. Discovery of the specific karyotypic abnormality of the Philadelphia (Ph) chromosome in the pathogenesis of CML has led to a better understanding of the disease and hence to an advancement of targeted therapeutics. Availability of imatinib as an accepted targeted therapy in newly diagnosed patients has changed the treatment paradigm in CML. The majority of CML patients in chronic phase achieve excellent and durable responses with standard-dose imatinib. Mechanisms of primary and secondary resistance to imatinib in CML have been extensively studied and newer tyrosine kinase inhibitors are now being evaluated for clinical use. It is important that at any time the CML treatment and response remain optimal and thus patients on imatinib require continuous monitoring for early detection of resistance. This review will discuss the treatment and guidelines for monitoring CML patients in the imatinib era.

Keywords: BCR-ABL; CML; imatinib; leukemia; tyrosine kinase inhibitors.

Figure 1

Mechanism of action of imatinib. A) The phosphorylation and activation of tyrosine residue after binding of adenosine triphosphate ATP in the kinase domain on the BCR-ABL oncoprotein. B) Prevention of phosphorylation and activation of tyrosine residue when imatinib binds to the kinase domain. Adapted with permission from Savage DG, Antman KH. Imatinib mesylate – a new oral targeted therapy. N Engl J Med. 2002;346:683–693. Copyright © 2002 Massuchusetts Medical Society. All rights reserved.