title: BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet.
abstract: Mutations in the Bcr-Abl kinase domain may cause, or contribute to, resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia patients. Recommendations aimed to rationalize the use of BCR-ABL mutation testing in chronic myeloid leukemia have been compiled by a panel of experts appointed by the European LeukemiaNet (ELN) and European Treatment and Outcome Study and are here reported. Based on a critical review of the literature and, whenever necessary, on panelists' experience, key issues were identified and discussed concerning: (1) when to perform mutation analysis, (2) how to perform it, and (3) how to translate results into clinical practice. In chronic phase patients receiving imatinib first-line, mutation analysis is recommended only in case of failure or suboptimal response according to the ELN criteria. In imatinib-resistant patients receiving an alternative TKI, mutation analysis is recommended in case of hematologic or cytogenetic failure as provisionally defined by the ELN. The recommended methodology is direct sequencing, although it may be preceded by screening with other techniques, such as denaturing-high performance liquid chromatography. In all the cases outlined within this abstract, a positive result is an indication for therapeutic change. Some specific mutations weigh on TKI selection.
authors.affiliation: Department of Hematology/Oncology L. e A. Seràgnoli, University of Bologna, Bologna, Italy. simona.soverini@tin.it
authors.forename: Simona
authors.initials: S
authors.lastname: Soverini
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: Franck E
authors.initials: FE
authors.lastname: Nicolini
authors.forename: Franz
authors.initials: F
authors.lastname: Gruber
authors.forename: Thoralf
authors.initials: T
authors.lastname: Lange
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Pane
authors.forename: Martin C
authors.initials: MC
authors.lastname: Müller
authors.forename: Thomas
authors.initials: T
authors.lastname: Ernst
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Rosti
authors.forename: Kimmo
authors.initials: K
authors.lastname: Porkka
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Nicholas C P
authors.initials: NC
authors.lastname: Cross
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
mesh_terms: D019058:Community Networks; D005060:Europe; D016044:Fusion Proteins, bcr-abl / Q000737:chemistry / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation; D010770:Phosphotransferases / Q000235:genetics; D017410:Practice Guidelines as Topic; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D017434:Protein Structure, Tertiary / Q000235:genetics; D012955:Societies, Medical / Q000331:legislation & jurisprudence / Q000458:organization & administration
chemical_list: D047428:Protein Kinase Inhibitors; D010770:Phosphotransferases; D016044:Fusion Proteins, bcr-abl