Oxidative status in essential thrombocythemia

Background: Oxidative stress (OS) is due to an excess of pro-oxidant species, like a Reactive Oxygen Species (ROS) and not counterbalanced by an adequate endogenous antioxidant molecules such as Reduced Glutathione (GSH). It has been demonstrated that it is involved in pathogenesis of atherothrombotic disease. Essential Thrombocythemia (ET), a BCR-ABL1-negative MPN, is characterised by increased platelet production and sustained thrombocytosis which can lead to thrombotic or hemorrhagic complications. Aims: To investigate oxidative status in ET. Methods: Thirty ET patients (13M/17F, age range 29-66 years) were recruited at our Hospital and compared to 26 healthy volunteers matched by age and gender (12M/14F, age range 28-69). All participants gave their informed consent. Serum ROS and whole blood GSH levels were measured by using a spectrophotometric method (dROMs test, Diacron International, Grosseto, Italy) and the HPLC method (Chromsystems Instruments & Chemicals, Munich, Germany) respectively. Reduced/oxidised glutathione ratio (GSH/GSSG) was also calculated. JAK2 mutational analysis was confirmed by direct sequencing (ABI PRISM 310 Genetic Analyzer, Applied Biosystems, Warrington, UK); for quantitative analysis of the allele burden of the JAK2 V617F mutation, we had to perform RQ-PCR using JAK2 MutaQuant™ (Ipsogen Inc., New Haven, CT). We compared levels of markers of OS between ET patients and healthy subjects using multiple linear regression models adjusted for gender, age (continuous), smoking (never, former, current), dyslipidemia (yes, no) and treatment with acetylsalicylc acid (yes, no). Results: Oxidative stress results of our study group are reported in Table 1. No significant differences of oxidative status parameters were found between JAK2 positive and JAK2 negative groups. Summary and Conclusions: Even if GSH levels were unusually augmented in ET, patients showed significantly increased levels of GSSG as well as a reduced GSH/GSSG ratio compared to the controls in place, therefore underlying that ET patients showed an altered oxidative status. Further studies are necessary to investigate if oxidative stress plays a role in ET thrombotic complications.