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.

Essential thrombocythemia (ET) is a BCR-ABL1-negative myeloproliferative neoplasm associated with thrombotic and haemorrhagic complications. Reactive oxygen species (ROS) overexpression induces a growth advantage to JAK2V617F-positive clones and, in association with a higher number of immature platelets, leukocytosis, and additional cardiovascular risk factors, leads to an increased risk for thrombotic events. We evaluated oxidative stress by measuring ROS levels and the total antioxidant capacity (TAC) in 62 ET patients and investigated the relationship between oxidative stress, JAK2V617F mutational status and the development of thrombotic events. We found higher oxidative stress levels in JAK2V617F-positive vs. JAK2V617F-negative ET cases with no significant differences between homozygous and heterozygous genotypes. Increased ROS levels and thrombotic events were more frequent in ET patients with old age at diagnosis, higher haematocrit levels or leukocytosis.

Évaluation du stress oxydatif chez les patients atteints de thrombocytémie essentielle sous traitement adapté au risque Introduction. La thrombocytémie essentielle (TE) est une maladie de la cellule-souche hématopoïétique caractérisée par une thrombocytose persistante dans le sang périphérique, une prolifération excessive des mégacaryocytes et une faible fibrose réticulinique dans la moelle osseuse. Il semble que le stress oxydatif soit impliqué dans le développement et la progression de la TE. L'objectif de l'étude est d'évaluer le niveau du stress oxydatif chez les patients atteints de TE sous traitement adapté au risque. Materiel et méthodes. 62 patients atteints de TE et 20 volontaires sains (consentement écrit obtenu) ont été inscrits. Le diagnostic a été fait second les critères OMS 2016 pour la TE (version révisée en 2016). Le

In the past decades, the involvement of reactive oxygen species (ROS) in health and disease has been intensely studied. Apart from their antimicrobial role in phagocytosis, ROS are also involved in a multitude of cellular processes, such as cell cycle progression, cellular motility or amplification of signaling factors. Many diseases are characterized by an overproduction of ROS or by deficient antioxidant systems, thus leading to oxidative stress (OxS) onset. The involvement of OxS in several types of solid cancers (prostate cancer, breast cancer, colorectal cancer and melanoma) and hematological malignancies (acute lymphoblastic leukemia, myelodysplastic syndromes, acute and chronic myeloid leukemia) has been proved. Recent studies have hypothesized that ROS derived from tumors can promote cell survival, migration, metastasis, proliferation and even drug-resistance according to the origin of the cancer. However, the involvement of OxS in carcinogenesis is far from being completely understood.

Chronic myeloid leukemia (CML) is a chronic myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome. Oxidative stress is involved in CML etiopathogenesis and disease progression, as well as the response to tyrosine kinase inhibitors (TKI) treatment. We evaluated oxidative stress levels in 47 CML patients vs. controls. The total antioxidant capacity (TAC) was measured using a FLUOstar Omega microplate reader (reagents from Sigma-Aldrich). Cellular reactive oxygen species (ROS) were evaluated using a CyFlow SPACE Sysmex flow-cytometer (reagents from Abcam). Oxidative stress levels were higher in CML patients vs. controls. The maximum TAC value and the minimum ROS value were recorded in CML patients with a BCR-ABL1 transcript value of 0.1-1%, suggesting that the production of plasma antioxidants progressively increases as a compensatory mechanism in CML patients undergoing TKI treatment in order to annihilate ROS. The pseudonormalization of the cell redox status observed in these patients could be an alarm signal prior to the development of resistance to TKI treatment or disease progression.