BCR-ABL mutant kinetics in CML patients treated with dasatinib.
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.
Nicolini
Franck E
FE
Hematology Department, Hôpital Edouard Herriot, 5 place d'Arsonval 69437 Lyon, France.
Chabane
Kaddour
K
Tigaud
Isabelle
I
Michallet
Mauricette
M
Magaud
Jean-Pierre
JP
Hayette
Sandrine
S
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*
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib