Disease-Specific Derangement of Circulating Endocannabinoids and N-Acylethanolamines in Myeloproliferative Neoplasms

Int J Mol Sci. 2020 May 11;21(9):3399. doi: 10.3390/ijms21093399.

Abstract

Growing evidence highlights the endocannabinoid (EC) system involvement in cancer progression. Lipid mediators of this system are secreted by hematopoietic cells, including the ECs 2-arachidonoyl-glycerol (2AG) and arachidonoyl-ethanolamide (AEA), the 2AG metabolite 1AG, and members of N-acylethanolamine (NAE) family-palmitoyl-ethanolamide (PEA) and oleoyl-ethanolamide (OEA). However, the relevance of the EC system in myeloproliferative neoplasms (MPN) was never investigated. We explored the EC plasma profile in 55 MPN patients, including myelofibrosis (MF; n = 41), polycythemia vera (PV; n = 9), and essential thrombocythemia (ET; n = 5) subclasses and in 10 healthy controls (HC). AEA, PEA, OEA, 2AG, and 1AG plasma levels were measured by LC-MS/MS. Overall considered, MPN patients displayed similar EC and NAE levels compared to HC. Nonetheless, AEA levels in MPN were directly associated with the platelet count. MF patients showed higher levels of the sum of 2AG and 1AG compared to ET and PV patients, higher OEA/AEA ratios compared to HC and ET patients, and higher OEA/PEA ratios compared to HC. Furthermore, the sum of 2AG and 1AG positively correlated with JAK2V617F variant allele frequency and splenomegaly in MF and was elevated in high-risk PV patients compared to in low-risk PV patients. In conclusion, our work revealed specific alterations of ECs and NAE plasma profile in MPN subclasses and potentially relevant associations with disease severity.

Keywords: N-acylethanolamines; endocannabinoids; essential thrombocythemia; myelofibrosis; myeloproliferative neoplasms; polycythemia vera.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amides / blood
  • Arachidonic Acids / blood
  • Chromatography, Liquid / methods
  • Endocannabinoids / blood*
  • Ethanolamines / blood*
  • Female
  • Glycerides / blood
  • Humans
  • Janus Kinase 2 / genetics
  • Male
  • Middle Aged
  • Mutation, Missense
  • Myeloproliferative Disorders / blood*
  • Myeloproliferative Disorders / diagnosis
  • Myeloproliferative Disorders / genetics
  • Oleic Acids / blood
  • Palmitic Acids / blood
  • Polycythemia Vera / blood*
  • Polycythemia Vera / diagnosis
  • Polycythemia Vera / genetics
  • Polyunsaturated Alkamides / blood
  • Primary Myelofibrosis / blood*
  • Primary Myelofibrosis / diagnosis
  • Primary Myelofibrosis / genetics
  • Tandem Mass Spectrometry / methods
  • Thrombocythemia, Essential / blood*
  • Thrombocythemia, Essential / diagnosis
  • Thrombocythemia, Essential / genetics

Substances

  • Amides
  • Arachidonic Acids
  • Endocannabinoids
  • Ethanolamines
  • Glycerides
  • N-acylethanolamines
  • Oleic Acids
  • Palmitic Acids
  • Polyunsaturated Alkamides
  • oleoylethanolamide
  • palmidrol
  • glyceryl 2-arachidonate
  • JAK2 protein, human
  • Janus Kinase 2
  • anandamide