Chronic myeloid leukemia (CML) is a progressive and often fatal 
myeloproliferative disorder. The hallmark of CML is an acquired chromosomal 
translocation known as the Philadelphia chromosome (Ph) that results in the 
synthesis of the BCR-ABL fusion protein, a constitutively active tyrosine kinase 
(TK). The introduction of imatinib, a TK inhibitor (TKI) specific for BCR-ABL, 
was a major breakthrough in CML therapy. Although most patients respond to 
first-line imatinib therapy, some experience a loss of response (resistance) or 
require treatment discontinuation because of toxicity (intolerance). In patients 
for whom standard-dose imatinib therapy (400 mg/day) fails, imatinib dose 
escalation (600-800 mg/day) is a second-line option. However, high-dose imatinib 
is not an appropriate approach for patients experiencing drug toxicity, and 
there remain questions over the durability of responses achieved with this 
strategy. Alternative second-line options include the newer TKIs dasatinib and 
nilotinib. A substantial amount of long-term data for these agents is available. 
Although both are potent and specific BCR-ABL TKIs, dasatinib and nilotinib 
exhibit unique pharmacologic profiles and response patterns relative to 
different patient characteristics, such as disease stage and BCR-ABL mutational 
status. To optimize therapeutic benefit, clinicians should select treatment 
based on each patient's historical response, adverse event tolerance level, and 
risk factors.