title: Dasatinib overrides imatinib resistance mediated by the F359I residue mutation in two patients with chronic myeloid leukemia.
abstract: Despite the beneficial effects of imatinib mesylate, some patients may either not respond or respond suboptimally. Here, we report two chronic myelogenous leukemia patients; one had a suboptimal response according to European LeukemiaNet criteria (a major molecular response was not achieved after 18 months of standard-dose imatinib therapy) and the other had failure with a standard dose of imatinib. At the time of the suboptimal response in patient 1 and the failure in patient 2, we were able to detect the F359I mutation in the BCR-ABL tyrosine kinase domain using DNA sequencing in both patients. Therefore, it was decided to change the therapeutic regimen to dasatinib at a dose of 100 mg once daily in both patients. This change resulted in the achievement of complete cytogenetic remission in patient 1 after 4 months and a major molecular response within 2 and 3 months in both patients. Detection of the F359I mutation in our two cases likely explains the suboptimal response to imatinib in case 1 and the failure in case 2. This implies that in such cases dasatinib should be considered to effectively suppress the mutated clones.
authors.affiliation: Department of Hematology, Faculty of Medicine, University of São Paulo, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Serpa
authors.forename: Sabri S
authors.initials: SS
authors.lastname: Sanabani
authors.forename: Pedro Enrique
authors.initials: PE
authors.lastname: Dorlhiac-Llacer
authors.forename: Luciana
authors.initials: L
authors.lastname: Nardinelli
authors.forename: Patricia
authors.initials: P
authors.lastname: de Barros Ferreira
authors.forename: Thays Fernanda Borges
authors.initials: TF
authors.lastname: Martins
authors.forename: Fernanda
authors.initials: F
authors.lastname: Seguro
authors.forename: Israel
authors.initials: I
authors.lastname: Bendit
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D001549:Benzamides; D004252:DNA Mutational Analysis; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics*; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D008297:Male; D020125:Mutation, Missense; D010879:Piperazines / Q000008:administration & dosage*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; 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; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib