Chronic myelogenous leukemia (CML) is a clonal hematopoietic disorder caused by 
the reciprocal translocation between chromosome 9 and 22. As a result of this 
translocation, a novel fusion gene, BCR-ABL, is created on Philadelphia (Ph) 
chromosome, and the constitutive activity of the BCR-ABL protein tyrosine kinase 
plays a critical role in the disease pathogenesis. Imatinib mesylate, a 
selective BCR-ABL tyrosine kinase inhibitor, was first given to a patient with 
CML in June 1998. Since then, it has continued to demonstrate remarkable 
efficacy in treating patients with CML. Based upon the results of early phase I 
and II studies, a phase III study (IRIS Study) that was randomized to first-line 
imatinib (400 mg/day) or to standard treatment with interferon+low-dose Ara-C, 
was conducted on 1,106 patients newly diagnosed (within 6 months) with 
chronic-phase CML. After median follow-up of 30 months, imatinib showed 
significantly superior tolerability, hematologic and cytogenetic responses 
(major cytogenetic response, 90%; complete cytogenetic response, 82%), and 
overall survival (95% without censoring allo-HSCT). Although imatinib is the 
first-line therapy and has changed the paradigm of CML treatment strategy, 
questions remain as to the meaning of cytogenetic and molecular response, 
curability, optimal dose, and relation with allo-HSCT.