Metabolite Profiling of the Plasma and Leukocytes of Chronic Myeloid Leukemia Patients
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- chronic myeloid leukemia, drug resistance, hydroxyurea, metabolomics, tyrosine kinase inhibitors,
- MeSH
- Amino Acids metabolism MeSH
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive blood metabolism MeSH
- Citric Acid Cycle drug effects MeSH
- Glycolysis drug effects MeSH
- Hydroxyurea pharmacology therapeutic use MeSH
- Imatinib Mesylate pharmacology therapeutic use MeSH
- Protein Kinase Inhibitors pharmacology MeSH
- Plasma chemistry metabolism MeSH
- Leukocytes chemistry metabolism MeSH
- Humans MeSH
- Metabolome * MeSH
- Metabolomics methods MeSH
- Drug Monitoring methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Amino Acids MeSH
- Hydroxyurea MeSH
- Imatinib Mesylate MeSH
- Protein Kinase Inhibitors MeSH
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 TKIs block the ATP-binding site; therefore, the signal pathways leading to malignant transformation are no longer active.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.
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