title: Advances in treatment of chronic myeloid leukemia with tyrosine kinase inhibitors: the evolving role of Bcr-Abl mutations and mutational analysis.
abstract: Over the last decade, the treatment of chronic myeloid leukemia has progressed tremendously. The first-generation tyrosine kinase inhibitor imatinib is now flanked by two second-generation molecules, dasatinib and nilotinib - and others are in advanced clinical development. One of the reasons for such intensive research on novel compounds is the problem of resistance, that is thought to be caused, in a proportion of cases, by point mutations in Bcr-Abl. In this article, the authors review how the biological and clinical relevance of Bcr-Abl mutations has evolved in parallel with the availability of more and more therapeutic options. The authors also discuss the practical relevance of Bcr-Abl mutation analysis and how this tool should best be integrated in the optimal clinical management of chronic myeloid leukemia patients.
authors.affiliation: Department of Hematology/Oncology L. e A. Seragnoli, S. Orsola-Malpighi Hospital, Via Massarenti 9, 40138, University of Bologna, Bologna, Italy. simona.soverini@tin.it
authors.forename: Simona
authors.initials: S
authors.lastname: Soverini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Rosti
authors.forename: Ilaria
authors.initials: I
authors.lastname: Iacobucci
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
mesh_terms: D001549:Benzamides; D002986:Clinical Trials as Topic; D004252:DNA Mutational Analysis; D019008:Drug Resistance, Neoplasm; D016313:Genes, abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use*
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; C498826:nilotinib