Metabolic assessment of a novel chronic myelogenous leukemic cell line and an imatinib resistant subline by 1H NMR spectroscopy

Brian J. Dewar, Kayvan Keshari, Rex Jeffries, Petras Dzeja, Lee M. Graves, Jeffrey M. Macdonald

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The goal of this study was to examine metabolic differences between a novel chronic myelogenous leukemic (CML) cell line, MyL, and a sub-clone, MyL-R, which displays enhanced resistance to the targeted Bcr-Abl tyrosine kinase inhibitor imatinib. 1H nuclear magnetic resonance (NMR) spectroscopy was carried out on cell extracts and conditioned media from each cell type. Both principal component analysis (PCA) and specific metabolite identification and quantification were used to examine metabolic differences between the cell types. MyL cells showed enhanced glucose removal from the media compared to MyL-R cells with significant differences in production rates of the glycolytic end-products, lactate and alanine. Interestingly, the total intracellular creatine pool (creatine + phosphocreatine) was significantly elevated in MyL-R compared to MyL cells. We further demonstrated that the MyL-R cells converted the creatine to phosphocreatine using non-invasive monitoring of perfused alginate-encapsulated MyL-R and MyL cells by in vivo 31P NMR spectroscopy and subsequent HPLC analysis of extracts. Our data demonstrated a clear difference in the metabolite profiles of drug-resistant and sensitive cells, with the biggest difference being an elevation of creatine metabolites in the imatinib-resistant MyL-R cells.

Original languageEnglish (US)
Pages (from-to)439-450
Number of pages12
JournalMetabolomics
Volume6
Issue number3
DOIs
StatePublished - 2010

Keywords

  • Chronic myelogenous leukemia
  • Creatine
  • Drug resistance
  • H NMR spectroscopy
  • Imatinib
  • Metabolomics

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Clinical Biochemistry

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