title: Optimising chronic myeloid leukaemia therapy in the face of resistance to tyrosine kinase inhibitors--a synthesis of clinical and laboratory data.
abstract: The introduction of imatinib, a tyrosine kinase inhibitor (TKI) that targets the BCR-ABL protein, has revolutionised the treatment of chronic myeloid leukaemia (CML), producing high rates of response that have been durable in many patients. However, because of intrinsic or acquired mechanisms of imatinib resistance, in addition to the persistence of leukaemic stem cells that are resistant to imatinib-induced apoptosis, imatinib treatment does not appear to be curative. Cytogenetic and molecular monitoring enable the identification of patients showing signs of treatment failure and can be used to guide choices regarding subsequent therapeutic options, including imatinib dose escalation, treatment with a secondary TKI or, in selected cases, allogeneic stem cell transplant (allo-SCT). Although these alternative therapies may overcome imatinib resistance, long-term remission or cure from CML is likely to require development of novel interventions that effectively eliminate CML stem cells (Ph+HSC).
authors.affiliation: Paul O'Gorman Leukaemia Research Centre, Section of Experimental Haematology, Faculty of Medicine, University of Glasgow, Gartnavel General Hospital, 1053 Great Western Road, Glasgow G12 0YN, United Kingdom. di10j@clinmed.gla.ac.uk
authors.forename: David A
authors.initials: DA
authors.lastname: Irvine
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Heaney
authors.forename: Tessa L
authors.initials: TL
authors.lastname: Holyoake
mesh_terms: D019468:Disease Management; D016903:Drug Monitoring; D019008:Drug Resistance, Neoplasm; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000628:therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors
chemical_list: D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases