title: Implications of BCR-ABL1 kinase domain-mediated resistance in chronic myeloid leukemia.
abstract: Patients with chronic myeloid leukemia develop resistance to both first-generation and second-generation tyrosine kinase inhibitors (TKIs) as a result of mutations in the kinase domain (KD) of BCR-ABL1. A wide range of BCR-ABL1 KD mutations that confer resistance to TKIs have been identified, and the T315I mutant has proven particularly difficult to target. This review summarizes the prevalence, impact, and prognostic implications of BCR-ABL1 KD mutations in patients with chronic myeloid leukemia who are treated with current TKIs and provides an overview of recent treatment guidelines and future trends for the detection of mutations.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. Electronic address: simona.soverini@tin.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Soverini
authors.affiliation: Department of Molecular Pathology, SA Pathology, Centre for Cancer Biology, Adelaide, Australia; School of Medicine, University of Adelaide, Adelaide, Australia; School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia.
authors.forename: Susan
authors.initials: S
authors.lastname: Branford
authors.affiliation: Hematology Department 1G, Centre Hospitalier Lyon Sud, Pierre Bénite, France.
authors.forename: Franck E
authors.initials: FE
authors.lastname: Nicolini
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Moshe
authors.initials: M
authors.lastname: Talpaz
authors.affiliation: Division of Hematology and Hematologic Malignancies, University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA.
authors.forename: Michael W N
authors.initials: MW
authors.lastname: Deininger
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.affiliation: III Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany.
authors.forename: Martin C
authors.initials: MC
authors.lastname: Müller
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Jerald P
authors.initials: JP
authors.lastname: Radich
authors.affiliation: Department of Hematology/Oncology, University of California, San Francisco, CA, USA.
authors.forename: Neil P
authors.initials: NP
authors.lastname: Shah
mesh_terms: D004252:DNA Mutational Analysis / Q000379:methods / Q000639:trends; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005544:Forecasting; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation; D017410:Practice Guidelines as Topic; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C581634:BCR-ABL1 fusion protein, human; D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl
keywords: BCR-ABL1; Chronic myeloid leukemia; Kinase domain; Mutations; Philadelphia chromosome; Resistance; Tyrosine kinase inhibitors