The potential relevance of the endocannabinoid, 2-arachidonoylglycerol, in diffuse large B-cell lymphoma
Jianqing Zhang1, Daniel Medina-Cleghorn2, Leon Bernal-Mizrachi3, Paige M. Bracci4, Alan Hubbard5, Lucia Conde1, Jacques Riby1, Daniel K. Nomura2, Christine F. Skibola1
1 Department of Epidemiology, School of Public Health, Comprehensive Cancer Center, University of Alabama at Birmingham, AL, USA
2 Department of Nutritional Sciences and Toxicology, University of California at Berkeley, CA, USA
3 Winship Cancer Institute of Emory University, Atlanta, GA, USA
4 Department of Epidemiology & Biostatistics, School of Medicine, University of California at San Francisco, CA, USA
5 School of Public Health, Division of Biostatistics, University of California at Berkeley, CA, USA
Christine F. Skibola, email:
Keywords: Endocannabinoids, 2-AG, DLBCL, lymphoma, obesity
Received: August 27, 2015 Accepted: January 22, 2016 Published: January 30, 2016
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, weperformed 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-<30kg/m2; 108%,P<0.01)and obese (BMI>30kg/m2; 118%, P<0.001)compared to those with a BMI<25 kg/m2. 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.