title: Simplifying procedure for prediction of resistance risk in CML patients - Test of sensitivity to TKI ex vivo.
abstract: Tyrosine kinase inhibitors (TKIs) targeting BCR-ABL have dramatically improved chronic myeloid leukemia therapy. While imatinib remains to be the first line therapy, about 30% of patients develop resistance or intolerance to this drug and are recommended to switch to other TKIs. Nilotinib and dasatinib are currently implemented into the first line therapy and other inhibitors have already entered the clinical practice. This opens further questions on how to select the best TKI for each patient not only during the therapy but also at diagnosis. The individualized therapy concept requires a reliable establishment of prognosis and prediction of response to the available TKIs. We tested the ex vivo sensitivity of patient primary leukocytes to imatinib, nilotinib and dasatinib - two concentrations of each inhibitor for 48h incubation - and we evaluated the usefulness of such tests for the clinical practice. Besides reflecting the actual sensitivity to the therapy, our optimized simple tests were able to predict the outcome in 90/87% of patients, for the next 12/24months, respectively. According to these results, the presented ex vivo testing could help clinicians to select the appropriate drug for each patient at diagnosis and also at any time of the therapy.
authors.affiliation: Dept. of Proteomics, Institute of Hematology and Blood Transfusion, U Nemocnice 1, Prague 2 128 20, Czech Republic. Electronic address: marketa.zackova@uhkt.cz.
authors.forename: Markéta
authors.initials: M
authors.lastname: Žáčková
authors.affiliation: Dept. of Proteomics, Institute of Hematology and Blood Transfusion, U Nemocnice 1, Prague 2 128 20, Czech Republic.
authors.forename: Tereza
authors.initials: T
authors.lastname: Macháčková-Lopotová
authors.affiliation: Dept. of Molecular Genetics, Institute of Hematology and Blood Transfusion, U Nemocnice 1, Prague 2 128 20, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Ondráčková
authors.affiliation: Dept. of Proteomics, Institute of Hematology and Blood Transfusion, U Nemocnice 1, Prague 2 128 20, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Kuželová
authors.affiliation: Clinical Dept., Institute of Hematology and Blood Transfusion, U Nemocnice 1, Prague 2 128 20, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Klamová
authors.affiliation: Dept. of Proteomics, Institute of Hematology and Blood Transfusion, U Nemocnice 1, Prague 2 128 20, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Moravcová
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000069439:Dasatinib / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology* / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C498826:nilotinib; D000069439:Dasatinib
keywords: Chronic myeloid leukemia; Early predictors; Resistance