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Lipidomic approach for stratification of acute myeloid leukemia patients.
PLoS ONE 12:e0168781 (2017)
The pathogenesis and progression of many tumors, including hematologic malignancies is highly dependent on enhanced lipogenesis. De novo fatty-acid synthesis permits accelerated proliferation of tumor cells by providing membrane components but these may also alter physicochemical properties of lipid bilayers, which can impact signaling or even increase drug resistance in cancer cells. Cancer type-specific lipid profiles would permit us to monitor and interpret actual effects of lipid changes, potential fingerprints of individual tumors to be explored as diagnostic markers. We have used the shotgun MS approach to identify lipid patterns in different types of acute myeloid leukemia (AML) patients that either show no karyotype change or belong to t(8; 21) or inv 16 types. Differences in lipidomes of t(8; 21) and inv(16) patients, as compared to AML patients without karyotype change, presented mostly as substantial modulation of ceramide/sphingolipid synthesis. Furthermore, between the t(8; 21) and all other patients we observed significant changes in physicochemical membrane properties. These were related to a marked alteration in lipid saturation levels. The discovered differences in lipid profiles of various AML types improve our understanding of the pathobiochemical pathways involved and may serve in the development of diagnostic tools.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Fatty-acid Synthase; Throughput Shotgun Lipidomics; Acute Myelogenous Leukemia; Mass-spectrometry; Breast-cancer; Glucosylceramide Synthase; Sphingolipid Metabolism; Multidrug-resistance; Cell-proliferation; Signaling Pathways
ISSN (print) / ISBN
1932-6203
Journal
PLoS ONE
Quellenangaben
Volume: 12,
Issue: 2,
Article Number: e0168781
Publisher
Public Library of Science (PLoS)
Publishing Place
Lawrence, Kan.
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Pancreatic Islet Research (IPI)