title: Therapeutic targeting of BCR-ABL: prognostic markers of response and resistance mechanism in chronic myeloid leukaemia.
abstract: Chronic myeloid leukemia (CML) is caused by the formation of the BCR-ABL fusion protein as a result of the t(9;22) chromosomal translocation. The elucidation of its molecular pathogenesis led to the identification of a therapeutic target and the subsequent synthesis and introduction of a small-molecule inhibitor for this target, imatinib. Because CML is the first disease successfully treated by targeted kinase inhibition, it served as a paradigm for discovery of disease mechanism and drug development in other diseases in which constitutive kinase expression plays a central role in pathogenesis. Despite the spectacular success of imatinib, not all CML patients derive great benefit from it. This review will cover some of the currently known prognostic markers of disease response and potential resistance mechanisms.
authors.affiliation: Haematology Department, SA Pathology (RAH Site), Centre for Cancer Biology, and University of Adelaide, Australia.
authors.forename: David T
authors.initials: DT
authors.lastname: Yeung
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Hughes
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000032:analysis / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl