title: Metabolite Profiling of the Plasma and Leukocytes of Chronic Myeloid Leukemia Patients.
abstract: The discovery of tyrosine kinase inhibitors (TKIs) brought a major breakthrough in the treatment of patients with chronic myeloid leukemia (CML). Pathogenetic CML events are closely linked with the Bcr-Abl protein with tyrosine kinase activity. TKIs block the ATP-binding site; therefore, the signal pathways leading to malignant transformation are no longer active. However, there is limited information about the impact of TKI treatment on the metabolome of CML patients. Using liquid chromatography mass spectrometric metabolite profiling and multivariate statistical methods, we analyzed plasma and leukocyte samples of patients newly diagnosed with CML, patients treated with hydroxyurea and TKIs (imatinib, dasatinib, nilotinib), and healthy controls. The global metabolic profiles clearly distinguished the newly diagnosed CML patients and the patients treated with hydroxyurea from those treated with TKIs and the healthy controls. The major changes were found in glycolysis, the citric acid cycle, and amino acid metabolism. We observed differences in the levels of amino acids and acylcarnitines between those patients responding to imatinib treatment and those who were resistant to it. According to our findings, the metabolic profiling may be potentially used as an additional tool for the assessment of response/resistance to imatinib.
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc , Hněvotínská 5, 779 00 Olomouc, Czech Republic.|Department of Clinical Biochemistry, University Hospital Olomouc , I. P. Pavlova 6, 775 20 Olomouc, Czech Republic.
authors.forename: Radana
authors.initials: R
authors.lastname: Karlíková
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc , Hněvotínská 5, 779 00 Olomouc, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Široká
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc , Hněvotínská 5, 779 00 Olomouc, Czech Republic.|Laboratory for Inherited Metabolic Disorders, Faculty of Medicine and Dentistry, Palacký University Olomouc , I. P. Pavlova 6, 775 20 Olomouc, Czech Republic.
authors.forename: David
authors.initials: D
authors.lastname: Friedecký
authors.affiliation: Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacký University Olomouc , I. P. Pavlova 6, 775 20 Olomouc, Czech Republic.
authors.forename: Edgar
authors.initials: E
authors.lastname: Faber
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc , Hněvotínská 5, 779 00 Olomouc, Czech Republic.
authors.forename: Marcela
authors.initials: M
authors.lastname: Hrdá
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc , Hněvotínská 5, 779 00 Olomouc, Czech Republic.|Department of Clinical Biochemistry, University Hospital Olomouc , I. P. Pavlova 6, 775 20 Olomouc, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Mičová
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc , Hněvotínská 5, 779 00 Olomouc, Czech Republic.
authors.forename: Iveta
authors.initials: I
authors.lastname: Fikarová
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc , Hněvotínská 5, 779 00 Olomouc, Czech Republic.|Department of Clinical Biochemistry, University Hospital Olomouc , I. P. Pavlova 6, 775 20 Olomouc, Czech Republic.|Department of Mathematical Analysis and Applications of Mathematics, Palacký University Olomouc , 17. Listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Alžběta
authors.initials: A
authors.lastname: Gardlo
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc , Hněvotínská 5, 779 00 Olomouc, Czech Republic.|Laboratory for Inherited Metabolic Disorders, Faculty of Medicine and Dentistry, Palacký University Olomouc , I. P. Pavlova 6, 775 20 Olomouc, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Janečková
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc , Hněvotínská 5, 779 00 Olomouc, Czech Republic.|Department of Clinical Biochemistry, University Hospital Olomouc , I. P. Pavlova 6, 775 20 Olomouc, Czech Republic.
authors.forename: Ivo
authors.initials: I
authors.lastname: Vrobel
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc , Hněvotínská 5, 779 00 Olomouc, Czech Republic.|Laboratory for Inherited Metabolic Disorders, Faculty of Medicine and Dentistry, Palacký University Olomouc , I. P. Pavlova 6, 775 20 Olomouc, Czech Republic.|Department of Clinical Biochemistry, University Hospital Olomouc , I. P. Pavlova 6, 775 20 Olomouc, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Adam
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D002952:Citric Acid Cycle / Q000187:drug effects; D016903:Drug Monitoring / Q000379:methods*; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology / Q000627:therapeutic use; D000068877:Imatinib Mesylate / Q000494:pharmacology / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000378:metabolism; D007962:Leukocytes / Q000737:chemistry / Q000378:metabolism; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D010949:Plasma / Q000737:chemistry / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate; D006918:Hydroxyurea
keywords: chronic myeloid leukemia; drug resistance; hydroxyurea; metabolomics; tyrosine kinase inhibitors