title: BCR-ABL mutations in chronic myeloid leukemia.
abstract: The advent of imatinib has been a major breakthrough in chronic myeloid leukemia (CML) treatment. A few patients treated with imatinib are either refractory to imatinib or eventually relapse. Resistance is frequently associated with mutations in the kinase domain of BCR-ABL. Over 100 point mutations coding for single amino acid substitutions in the BCR-ABL kinase domain have been isolated from CML patients resistant to imatinib treatment. Most reported mutants are rare, whereas 7 mutated residues comprise two-thirds of all mutations detected. BCR-ABL mutations affect amino acids involved in imatinib binding or in regulatory regions of the BCR-ABL kinase domain, resulting in decreased sensitivity to imatinib while retaining aberrant kinase activity. The early detection of BCR-ABL mutants during therapy may aid in risk stratification as well as molecularly based treatment decisions.
authors: Klinik für Innere Medizin II, Universitätsklinikum Jena, Erlanger Allee 101, 07740 Jena, Germany.
authors: Thomas
authors: T
authors: Ernst
authors: Paul
authors: P
authors: La Rosée
authors: Martin C
authors: MC
authors: Müller
authors: Andreas
authors: A
authors: Hochhaus
mesh_terms: D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D017354:Point Mutation; D017434:Protein Structure, Tertiary
chemical_list: D016044:Fusion Proteins, bcr-abl