Metabolite Profiling of the Plasma and Leukocytes of Chronic Myeloid Leukemia Patients
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
- Klíčová slova
- chronic myeloid leukemia, drug resistance, hydroxyurea, metabolomics, tyrosine kinase inhibitors,
- MeSH
- aminokyseliny metabolismus MeSH
- chronická myeloidní leukemie krev metabolismus MeSH
- citrátový cyklus účinky léků MeSH
- glykolýza účinky léků MeSH
- hydroxymočovina farmakologie terapeutické užití MeSH
- imatinib mesylát farmakologie terapeutické užití MeSH
- inhibitory proteinkinas farmakologie MeSH
- krevní plazma chemie metabolismus MeSH
- leukocyty chemie metabolismus MeSH
- lidé MeSH
- metabolom * MeSH
- metabolomika metody MeSH
- monitorování léčiv metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- aminokyseliny MeSH
- hydroxymočovina MeSH
- imatinib mesylát MeSH
- inhibitory proteinkinas 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 TKIs block the ATP-binding site; therefore, the signal pathways leading to malignant transformation are no longer active.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.
Citace poskytuje Crossref.org
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