title: Dasatinib treatment can overcome imatinib and nilotinib resistance in CML patient carrying F359I mutation of BCR-ABL oncogene.
abstract: Point mutations of bcr-abl tyrosine kinase are the most frequent causes of imatinib resistance in chronic myeloid leukaemia (CML) patients. In most CML cases with BCR-ABL mutations leading to imatinib resistance the second generation of tyrosine kinase inhibitors (TKI- e.g. nilotinib or dasatinib) may be effective. Here, we report a case of a CML patient who during imatinib treatment did not obtain clinical and cytogenetic response within 12 months of therapy. The sequencing of BCR-ABL kinase domains was performed and revealed the presence of a F359I point mutation (TTC-to-ATC nucleotide change leading to Phe-to-Ile amino acid substitution). After 1 month of nilotinib therapy a rapid progression of clinical symptoms was observed. In the presence of the F359I point mutation only dasatinib treatment overcame imatinib and nilotinib resistance.
authors.affiliation: Department of Hematology, Poznan University of Medical Sciences, Poznań, Poland. marta.baranska@onet.eu
authors.forename: Marta
authors.initials: M
authors.lastname: Barańska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Lewandowski
authors.forename: Michał
authors.initials: M
authors.lastname: Gniot
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Iwoła
authors.forename: Maria
authors.initials: M
authors.lastname: Lewandowska
authors.forename: Mieczysław
authors.initials: M
authors.lastname: Komarnicki
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D016313:Genes, abl; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D017354:Point Mutation; D011743:Pyrimidines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; C498826:nilotinib; D000069439:Dasatinib