Chronic myeloid leukemia (CML) is the first human malignancy for which the 
promise of targeted therapy has come true. CML is invariably associated with a 
specific genetic lesion--the t(9;22) chromosomal translocation. As a consequence 
of this translocation, a BCR-ABL fusion gene is formed on the 22q- derivative 
(traditionally known as the Philadelphia chromosome) and the deregulated 
tyrosine kinase activity of the protein encoded by this gene has been shown to 
be both necessary and sufficient for initiation and maintenance of the disease. 
Imatinib mesylate, an orally available tyrosine kinase inhibitor that targets 
Bcr-Abl, entered clinical evaluation in 1998. Its efficacy surpassed almost 
everyone's predictions, and the observation of high response rates and favorable 
toxicity profile associated with imatinib therapy led to its approval as 
first-line treatment for all newly diagnosed CML patients over an exceptionally 
short period of time. The 6-year results of the Phase III trial have recently 
been reported and confirm durability of responses and declining incidence of 
adverse events over time, although, at present, occurrence of unexpected side 
effects in the long term cannot be excluded. Although imatinib does not 'cure' 
CML and has to be administered chronically to patients, it has revolutionized 
both outcome and quality of life of CML patients.