Optimizing therapy of chronic myeloid leukemia

Chronic myeloid leukemia (CML) is caused by Bcr-Abl, a constitutively active tyrosine kinase that is the result of a reciprocal translocation between chromosomes 9 and 22 and cytogenetically evident as the Philadelphia chromosome. Imatinib (Glivec, Gleevec), a specific small molecule inhibitor of Bcr-Abl, has become the standard drug therapy for CML, and has dramatically diminished the use of allogeneic stem cell transplantation. Despite unprecedented rates of complete cytogenetic response, residual disease remains detectable in the majority of patients, suggesting that imatinib fails to eradicate leukemic stem cells. In this publication, the current perspectives for CML patients treated with imatinib are reviewed, focusing on the results of both standard and high-dose therapy. Monitoring of time-dependent prognostic factors is reviewed. The reasons imatinib may not be able to eradicate the disease are discussed, and potential strategies to achieve disease elimination are presented. Lastly, resistance to imatinib and the potential of second-generation Abl kinase inhibitors in the setting of clinical resistance are considered.