title: Resistance to tyrosine kinase inhibition therapy for chronic myelogenous leukemia: a clinical perspective and emerging treatment options.
abstract: The development of tyrosine kinase inhibitors (TKIs) has led to extended lifespans for many patients with chronic myelogenous leukemia (CML). However, 20% to 30% of patients fail to respond, respond suboptimally, or experience disease relapse after treatment with imatinib. A key factor is drug resistance. The molecular mechanisms implicated in this resistance include those that involve upregulation or mutation of BCR-ABL kinase and those that are BCR-ABL independent. The clinical consequences of these molecular mechanisms of resistance for disease pathogenesis remain open for debate. This review summarizes the molecular mechanisms and clinical consequences of TKI resistance and addresses the current and future treatment approaches for patients with TKI-resistant CML.
authors.affiliation: The University of Texas, MD Anderson Cancer Center, Houston, TX. Electronic address: ejabbour@mdanderson.org.
authors.forename: Elias J
authors.initials: EJ
authors.lastname: Jabbour
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
mesh_terms: D019943:Amino Acid Substitution; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl
keywords: BCR-ABL mutations; Molecular mechanisms; T315I
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