Marini Cecilia, Cossu Vanessa, Lanfranchi Francesco, Carta Sonia, Vitale Francesca, D'Amico Francesca, Bauckneht Matteo, Morbelli Silvia, Donegani Maria Isabella, Chiola Silvia, Raffa Stefano, Sofia Luca, Di Raimondo Tania, Ballerini Filippo, Ghiggi Chiara, Durando Paolo, Ravera Silvia, Riondato Mattia, Orengo Anna Maria, Bruno Silvia, Chiesa Sabrina, Sambuceti Gianmario
Institute of Molecular Bioimaging and Physiology (IBFM), National Research Council (CNR), 20054 Milan, Italy.
IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy.
Cancers (Basel). 2023 Jul 7;15(13):3533. doi: 10.3390/cancers15133533.
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.
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, F-fluoro-deoxyglucose uptake was estimated in the myocardium and skeletal muscles.
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.
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.
先前的研究报道了初治霍奇金淋巴瘤（HL）患者外周血单核细胞（PBMC）中的线粒体和内质网氧化还原应激。在此，我们评估这种反应是否也适用于非HL（NHL）患者，以及氧化损伤是PBMC的选择性特征，还是也会影响未直接参与炎症反应的组织。
对28例HL、9例弥漫性大B细胞淋巴瘤、8例侵袭性较低的NHL患者以及45例对照者的分离PBMC进行流式细胞术，以评估氧化还原应激和葡萄糖类似物2-NBDG的摄取。该分析辅以丙二醛（MDA）水平测定以及葡萄糖-6磷酸脱氢酶和己糖-6磷酸脱氢酶（H6PD）的酶活性测定。在所有淋巴瘤患者中，评估心肌和骨骼肌中的F-氟脱氧葡萄糖摄取情况。
仅HL患者的线粒体活性氧生成、MDA水平以及H6PD活性和2-NBDG摄取增加。同样，HL患者心肌中的FDG滞留高于其他组，而骨骼肌中的示踪剂摄取情况相似。
相对于两个NHL组，HL患者PBMC的氧化还原应激更为明显。这种现象与H6PD活性增加一致，且这种增加也延伸至心肌。
