Chronic myeloid leukemia cells contain a BCR-ABL oncoprotein with an enhanced 
tyrosine kinase activity, which is considered to be the principal 'cause' of the 
leukemia. Though the precise mechanisms underlying the leukemogenesis remains 
enigmatic, the use of imatinib to inhibit the dysregulated kinase activity has 
proved remarkably successful in clinical practice. Imatinib was the first small 
molecule developed to inhibit BCR-ABL tyrosine kinase activity and its success 
introduced the current era of molecularly targeted therapies for a number of 
other malignancies. In patients with chronic myeloid leukaemia who develop 
resistance to imatinib, the Bcr-Abl signaling pathway is often re-established. 
This has led to the emergence of a number of alternative treatment strategies 
designed to target the leukemic cell which are resistant to imatinib.