Abstract

Essential thrombocythemia (ET) is a Philadelphia-negative chronic myeloproliferative neoplasm characterized by acquired somatic mutations: JAK2, CALR or MPL. It is associated with low-grade chronic inflammation, oxidative stress, overproduction of reactive oxygen species (ROS) and antioxidant deficiency. In ET, chronic inflammation and oxidative stress contribute to the genomic instability, the clonal evolution to myelofibrosis and the leukemic transformation. We evaluated ROS levels and the total antioxidant capacity (TAC) in 62 ET patients and investigated the relationship between ROS, TAC, chronic inflammation, leukocytosis, JAK2V617F mutation, and disease progression to myelofibrosis or leukemic transformation. We observed increased levels of ROS and inflammation markers and a decreased TAC in ET patients vs. controls. The acute myeloid leukaemia transformation associated increased levels of oxidative stress and inflammation markers and increased leukocyte counts, while myelofibrosis progression associated an increase in ROS and serum ferritin. Keywords: essential thrombocythemia, reactive oxygen species, inflammation, JAK2V617F

Highlights

  • Essential thrombocythemia (ET) is a Philadelphia-negative chronic myeloproliferative neoplasm characterized by acquired somatic mutations: JAK2, CALR or MPL

  • = 2.73 mM/L vs. 2.60 mM/L; p

  • We found positive weak correlations between oxidative stress markers and fibrinogen, C-reactive protein (CRP), serum ferritin and a moderate positive correlation between oxidative stress -leukocyte count and NLR, respectively

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Summary

Introduction

Essential thrombocythemia (ET) is a Philadelphia-negative chronic myeloproliferative neoplasm characterized by acquired somatic mutations: JAK2, CALR or MPL It is associated with low-grade chronic inflammation, oxidative stress, overproduction of reactive oxygen species (ROS) and antioxidant deficiency. We evaluated ROS levels and the total antioxidant capacity (TAC) in 62 ET patients and investigated the relationship between ROS, TAC, chronic inflammation, leukocytosis, JAK2V617F mutation, and disease progression to myelofibrosis or leukemic transformation. Recent studies have shown that Philadelphia-negative MPNs (essential thrombocythemia, polycythaemia vera and primary myelofibrosis) are associated with low-grade chronic inflammation, oxidative stress, overproduction of reactive oxygen species (ROS) and antioxidant defence deficiency. The aim of the study was to evaluate oxidative stress levels in patients with ET and to investigate the relationship between ROS, TAC, chronic inflammation parameters, leukocytosis, JAK2V617F mutation and progression of disease to myelofibrosis or leukemic transformation. Informed consent was obtained from all subjects involved, the study protocol had the approval of the Ethics Committee of the University of Medicine and Pharmacy of Craiova (approval no. 79/23.02.2017) and was carried out in accordance with the standards imposed by the Declaration of Helsinki and the European Union 679/2016 regulation

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