title: The potential relevance of the endocannabinoid, 2-arachidonoylglycerol, in diffuse large B-cell lymphoma.
abstract: Diffuse large B-cell lymphoma is an aggressive, genetically heterogenerous disease and the most common type of non-Hodgkin lymphoma among adults. To gain further insights into the etiology of DLBCL and to discover potential disease-related factors, we performed a serum lipid analysis on a subset of individuals from a population-based NHL case-control study. An untargeted mass-spectrometry-based metabolomics platform was used to analyze serum samples from 100 DLBCL patients and 100 healthy matched controls. Significantly elevated levels of the endocannabinoid, 2-arachidonoylglycerol (2-AG), were detected in the serum of DLBCL patients (121%, P < 0.05). In the male controls, elevated 2-AG levels were observed in those who were overweight (BMI ≥ 25 - < 30 kg/m2; 108%, P < 0.01) and obese (BMI ≥ 30 kg/m(2); 118%, P < 0.001) compared to those with a BMI < 25 kg/m(2). DLBCL cell lines treated with exogenous 2-AG across a range of concentrations, exhibited heterogenous responses: proliferation rates were markedly higher in 4 cell lines by 22%-68% (P < 0.001) and lower in 8 by 20%-75% (P < 0.001). The combined findings of elevated 2-AG levels in DLBCL patients and the proliferative effects of 2-AG on a subset of DLBCL cell lines suggests that 2-AG may play a potential role in the pathogenesis or progression of a subset of DLBCLs.
authors.affiliation: Department of Epidemiology, School of Public Health, Comprehensive Cancer Center, University of Alabama at Birmingham, AL, USA.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Nutritional Sciences and Toxicology, University of California at Berkeley, CA, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Medina-Cleghorn
authors.affiliation: Winship Cancer Institute of Emory University, Atlanta, GA, USA.
authors.forename: Leon
authors.initials: L
authors.lastname: Bernal-Mizrachi
authors.affiliation: Department of Epidemiology & Biostatistics, School of Medicine, University of California at San Francisco, CA, USA.
authors.forename: Paige M
authors.initials: PM
authors.lastname: Bracci
authors.affiliation: School of Public Health, Division of Biostatistics, University of California at Berkeley, CA, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Hubbard
authors.affiliation: Department of Epidemiology, School of Public Health, Comprehensive Cancer Center, University of Alabama at Birmingham, AL, USA.
authors.forename: Lucia
authors.initials: L
authors.lastname: Conde
authors.affiliation: Department of Epidemiology, School of Public Health, Comprehensive Cancer Center, University of Alabama at Birmingham, AL, USA.
authors.forename: Jacques
authors.initials: J
authors.lastname: Riby
authors.affiliation: Department of Nutritional Sciences and Toxicology, University of California at Berkeley, CA, USA.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Nomura
authors.affiliation: Department of Epidemiology, School of Public Health, Comprehensive Cancer Center, University of Alabama at Birmingham, AL, USA.
authors.forename: Christine F
authors.initials: CF
authors.lastname: Skibola
keywords: 2-AG; DLBCL; endocannabinoids; lymphoma; obesity