Advances in the biology and therapy of patients with chronic myeloid leukaemia.

Chronic myelogenous leukaemia (CML) is a progressive and often fatal haematopoietic neoplasm. The Bcr-Abl tyrosine kinase inhibitor imatinib mesylate represented a major therapeutic advance over conventional CML therapy, with more than 90% of patients obtaining complete haematologic response and 70-80% of patients achieving a complete cytogenetic response. Resistance to imatinib represents a clinical challenge and is often a result of point mutations causing a conformation change in Bcr-Abl, which impairs imatinib binding. Novel targeted agents designed to overcome imatinib resistance include dasatinib, nilotinib, bosutinib and others. Other approaches are exploring combination therapy, with agents affecting different oncogenic pathways and immune modulation. Herein, we review some of these targeted therapies, particularly those for which clinical data are already available.