title: Mechanisms and novel approaches in overriding tyrosine kinase inhibitor resistance in chronic myeloid leukemia.
abstract: Chronic myeloid leukemia is a stem cell-initiated but progenitor-driven disease induced by the BCR-ABL oncogene. Tyrosine kinase inhibitors (TKIs) were introduced in the late 1990s and have revolutionized the management of chronic myeloid leukemia in chronic phase. The majority of patients can now expect to live a normal life as long as they continue to comply with TKI treatment. However, in a significant proportion of cases TKI resistance develops over time, requiring a switch of therapy. The most frequent mechanism for drug resistance is the development of kinase domain mutations that reduce or completely ablate drug efficacy. Fortunately, the last 10 years have seen an impressive array of new drugs, some modeled on the mechanism of action of imatinib, others employing more novel approaches, for these patients.
authors.affiliation: Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 OYN, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Karvela
authors.forename: G Vignir
authors.initials: GV
authors.lastname: Helgason
authors.forename: Tessa L
authors.initials: TL
authors.lastname: Holyoake
mesh_terms: D001549:Benzamides; D002986:Clinical Trials as Topic; D019468:Disease Management; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000235:genetics; D042822:Genomic Instability; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D022423:Myeloid Cells / Q000378:metabolism; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D039904:Pluripotent Stem Cells / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D035703:Therapies, Investigational; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl