Current treatment approaches for chronic myelogenous leukemia

Chronic myelogenous leukemia (CML) is a clonal hematopoietic stem cell disorder that progresses through distinct phases characterized by progressive loss of the differentiation of the malignant clone. Over the past 4 decades, it has been established that the Bcr-Abl protein, created as a consequence of a (9:22) chromosomal translocation, is the cause of the disease. Bcr-Abl functions as a constitutively activated tyrosine kinase, and this kinase activity is absolutely required for the transforming function of the Bcr-Abl protein. Thus, a specific inhibitor of the Bcr-Abl tyrosine kinase would be predicted to be an effective and selective therapeutic agent for CML. STI571, an Abl-specific tyrosine kinase inhibitor, has shown remarkable activity in all phases of CML. The clinical features, molecular pathogenesis, and current treatment options of CML are reviewed along with the development of STI571, the phase I clinical results, and the application of this paradigm to other malignancies.