title: BCR-ABL mutant kinetics in CML patients treated with dasatinib.
abstract: Dasatinib is efficient in vitro against most of CML cells harboring ABL kinase domain mutations and induces high rates of response in imatinib-resistant CML patients. Here, we monitored the mutated BCR-ABL transcripts during the follow-up of 12 CML patients treated with dasatinib. We identified four groups of patients based on their sensitivity to dasatinib. Clinical responses were correlated to the in vitro sensitivity of BCR-ABL mutants to dasatinib, however, some discrepancies were observed in a subfraction of CML patients, suggesting subtle differences between in vitro observations and clinical entities and/or the onset of other mechanisms responsible for dasatinib resistance.
authors.affiliation: Hematology Department, Hôpital Edouard Herriot, 5 place d'Arsonval 69437 Lyon, France.
authors.forename: Franck E
authors.initials: FE
authors.lastname: Nicolini
authors.forename: Kaddour
authors.initials: K
authors.lastname: Chabane
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tigaud
authors.forename: Mauricette
authors.initials: M
authors.lastname: Michallet
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Magaud
authors.forename: Sandrine
authors.initials: S
authors.lastname: Hayette
mesh_terms: D000328:Adult; D000368:Aged; D001549:Benzamides; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000008:administration & dosage; D012150:Polymorphism, Restriction Fragment Length; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D013844:Thiazoles / Q000008:administration & dosage*
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib