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

International Journal of Molecular Sciences

Dorian Forte¹  Giuseppe Auteri¹  Lucia Catani¹  Carolina Terragna¹  Martina Barone¹  Daniela Bartoletti¹  Giulia Corradi¹  Marina Martello¹  Michele Cavo¹  Francesca Palandri²  Emanuela Ottaviani²  Antonio Curti²  Uberto Pagotto³  Flaminia Fanelli³  Marco Mezzullo³ 

[1] Institute of Hematology “L. e A. Seràgnoli”, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), School of Medicine, University of Bologna, 40138 Bologna, Italy;Institute of Hematology “L. e A. Seràgnoli”, Department of Oncology and Hematology, University-Hospital S.Orsola, 40138 Bologna, Italy;Unit of Endocrinology and Prevention and Care of Diabetes, Center for Applied Biomedical Research, Department of Medical and Surgical Sciences, University of Bologna, University-Hospital S.Orsola, 40138 Bologna, Italy;

关键词: endocannabinoids;    N-acylethanolamines;    myeloproliferative neoplasms;    myelofibrosis;    polycythemia vera;    essential thrombocythemia;   

DOI  :  10.3390/ijms21093399

来源: DOAJ

【 摘 要 】

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 JAK2^V617F 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.

【 授权许可】

Unknown