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A role for oleoylethanolamide in chronic lymphocytic leukemia

Leukemia volume 28, pages 1381–1387 (2014)Cite this article

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Abstract

Oleoylethanolamide (OEA) is a bioactive lipid that stimulates nuclear and G protein-coupled receptors and regulates appetite and fat metabolism. It has not previously been shown to have a role in cancer. However, a mass spectrometry-based lipidomics platform revealed the presence of high amounts of OEA in the plasma of chronic lymphocytic leukemia (CLL) patients compared with normal donors. CLL cells produced OEA and the magnitude of plasma OEA levels was related directly to the circulating leukemic cell number. OEA from CLL cells was increased by URB-597, an inhibitor of fatty acid amide hydrolase (FAAH), and decreased by inflammatory mediators that downregulate expression of N-acylphosphatidylethanolamine-specific phospholipase D (NAPE-PLD). These enzymes degrade and synthesize OEA, respectively. Nonphysiologic doses of OEA prevented spontaneous apoptosis of CLL cells in a receptor-independent manner that was mimicked by its free fatty acid (FFA) derivative oleate. However, OEA-containing supernatants from CLL cells induced lipolysis in adipocytes, lipid products from adipocytes protected CLL cells from cytotoxic chemotherapy, and increased levels of FFAs were found in CLL plasma that correlated with OEA. We suggest OEA is a lipolytic factor produced by CLL cells to fuel their growth with a potential role in drug resistance and cancer cachexia.

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Acknowledgements

This work was supported by the Canadian Cancer Society (grant # 701630), Canadian Institutes of Health Research (CIHR) (grants MOP-110952 and MOP-130479), Leukemia and Lymphoma Society of Canada, and the Coxford family Research Fund (to DES).

Author information

Authors and Affiliations

  1. Nestlé Institute of Health Sciences, Lausanne, Switzerland

    M Masoodi

  2. Medical Research Council, Cambridge, UK

    M Masoodi & M Eiden

  3. Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada

    M Masoodi

  4. Biology Platform, Sunnybrook Research Institute, Toronto, Ontario, Canada

    E Lee, A Bahlo, Y Shi & D E Spaner

  5. Metabolomx, Mountain View, CA, USA

    M Eiden

  6. School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada

    R B Ceddia

  7. Inception Sciences, Inc., San Diego, CA, USA

    C Baccei & P Prasit

  8. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

    D E Spaner

  9. Sunnybrook Odette Cancer Center, Toronto, Ontario, Canada

    D E Spaner

  10. Department of Medicine, University of Toronto, Toronto, Ontario, Canada

    D E Spaner

  11. Department of Immunology, University of Toronto, Toronto, Ontario, Canada

    D E Spaner

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  1. M Masoodi
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Correspondence to D E Spaner.

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Masoodi, M., Lee, E., Eiden, M. et al. A role for oleoylethanolamide in chronic lymphocytic leukemia. Leukemia 28, 1381–1387 (2014). https://doi.org/10.1038/leu.2014.10

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