Divergent Oxidative Stress in Normal Tissues and Inflammatory Cells in Hodgkin and Non-Hodgkin Lymphoma

Abstract

Background: Previous studies reported mitochondrial and endoplasmic reticulum redox stress in peripheral blood mononucleated cells (PBMCs) of treatment-naïve Hodgkin lymphoma (HL) patients. Here, we assessed whether this response also applies to non-HL (NHL) patients, and whether the oxidative damage is a selective feature of PBMCs or, rather, also affects tissues not directly involved in the inflammatory response. Methods: Isolated PBMCs of 28 HL, 9 diffuse large B cell lymphoma, 8 less aggressive-NHL, and 45 controls underwent flow cytometry to evaluate redox stress and uptake of the glucose analogue 2-NBDG. This analysis was complemented with the assay of malondialdehyde (MDA) levels and enzymatic activity of glucose-6P-dehydrogenase and hexose-6P-dehydrogenase (H6PD). In all lymphoma patients, 18F-fluoro-deoxyglucose uptake was estimated in the myocardium and skeletal muscles. Results: Mitochondrial reactive oxygen species generation and MDA levels were increased only in HL patients as well as H6PD activity and 2-NBDG uptake. Similarly, myocardial FDG retention was higher in HL than in other groups as opposed to a similar tracer uptake in the skeletal muscle. Conclusions: Redox stress of PBMCs is more pronounced in HL with respect to both NHL groups. This phenomenon is coherent with an increased activity of H6PD that also extends to the myocardium.