Recent advances in Philadelphia chromosome-positive malignancies: the potential role of arsenic trioxide.

Chronic myelogenous leukemia (CML) is characterized by the presence of the Bcr-Abl fusion gene, which encodes a constitutively active tyrosine kinase that has been strongly implicated as the sole oncogenic abnormality in early-stage CML. Treatment with the specific tyrosine kinase inhibitor imatinib mesylate has achieved excellent results in CML, at all stages of the disease. However, limitations to the successful use of imatinib mesylate as a single agent include the problem of resistance, seen chiefly in patients with advanced-phase disease. This review summarizes the clinical results to date with imatinib mesylate and briefly discusses the problem of resistance before describing potential strategies, including the use of combination therapy. In particular, the rationale for combination therapy with arsenic trioxide will be examined.