Current treatment approaches for chronic myelogenous leukemia

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