Iurlo Alessandra, De Giuseppe Rachele, Sciumè Mariarita, Cattaneo Daniele, Fermo Elisa, De Vita Claudia, Consonni Dario, Maiavacca Rita, Bamonti Fabrizia, Gianelli Umberto, Cortelezzi Agostino
Oncohematology Division, IRCCS Ca' Granda-Maggiore Policlinico Hospital Foundation, University of Milan, Milano, Italy.
Oncohematology Unit of the Elderly, IRCCS Ca' Granda-Maggiore Policlinico Hospital Foundation, Milano, Italy.
Hematol Oncol. 2017 Sep;35(3):335-340. doi: 10.1002/hon.2264. Epub 2015 Oct 6.
Oxidative stress (OS), due to pro-oxidant species [reactive oxygen species (ROS)] excess not counterbalanced by endogenous antioxidant molecules [e.g., reduced glutathione (GSH)], is involved in the pathogenesis of human cancers, but few data are available on essential thrombocythemia (ET). This study aims to investigate OS in ET off-therapy patients. Thirty ET treatment-naïve patients were compared with 26 age-matched and gender-matched controls. Serum ROS, urinary 8-hydroxydeoxyguanosine, full blood GSH levels, and reduced/oxidized GSH ratio (GSH/GSSG) were measured. Data were adjusted for gender, age, JAK2 mutational status, smoking, dyslipidemia, or hypercholesterolemia requiring drug therapy, antiplatelet therapy, treatment with acetylsalicylic acid, high-sensitive C-reactive protein levels, and absolute monocyte count. ROS and GSH levels were increased in both patients and controls. Patients showed increased GSSG (p = 0.05), reduced GSH/GSSG ratio (p = 0.08), and similar 8-hydroxydeoxyguanosine levels when compared with controls. No differences in OS parameters were found between JAK2-positive and JAK2-negative patients. Confounding factors did not modify the results. Our study suggests an OS condition in a cohort of treatment-naïve ET patients, not associated with JAK2 mutational status or with chronic inflammation situation. GSH/GSSG ratio, altered in ET patients because of increased GSSG levels, showed the presence of higher GSH levels in ET than controls as a possible compensatory mechanism of an excess of pro-oxidant production. Copyright © 2015 John Wiley & Sons, Ltd.
氧化应激（OS）是由于促氧化物质[活性氧（ROS）]过量而未被内源性抗氧化分子[如还原型谷胱甘肽（GSH）]抵消所致，它参与人类癌症的发病机制，但关于原发性血小板增多症（ET）的数据较少。本研究旨在调查未经治疗的ET患者的氧化应激情况。将30例未经治疗的ET患者与26例年龄和性别匹配的对照组进行比较。测量血清ROS、尿8-羟基脱氧鸟苷、全血GSH水平以及还原型/氧化型GSH比值（GSH/GSSG）。对数据进行了性别、年龄、JAK2突变状态、吸烟、血脂异常或需要药物治疗的高胆固醇血症、抗血小板治疗、阿司匹林治疗、高敏C反应蛋白水平和绝对单核细胞计数的校正。患者和对照组的ROS和GSH水平均升高。与对照组相比，患者的GSSG升高（p = 0.05），GSH/GSSG比值降低（p = 0.08），8-羟基脱氧鸟苷水平相似。JAK2阳性和JAK2阴性患者之间的氧化应激参数没有差异。混杂因素未改变结果。我们的研究表明，一组未经治疗的ET患者存在氧化应激状态，这与JAK2突变状态或慢性炎症情况无关。由于GSSG水平升高，ET患者的GSH/GSSG比值发生改变，表明ET患者的GSH水平高于对照组，这可能是促氧化剂产生过多的一种代偿机制。版权所有© 2015 John Wiley & Sons, Ltd.
