Abstract
Thrombosis is a major cause of morbimortality in patients with chronic Philadelphia chromosome-negative myeloproliferative neoplasms (MPN). In the last decade, multiple lines of evidence support the role of leukocytes in thrombosis of MPN patients. Besides the increase in the number of cells, neutrophils and monocytes of MPN patients show a pro-coagulant activated phenotype. Once activated, neutrophils release structures composed of DNA, histones, and granular proteins, called extracellular neutrophil traps (NETs), which in addition to killing pathogens, provide an ideal matrix for platelet activation and coagulation mechanisms. Herein, we review the published literature related to the involvement of NETs in the pathogenesis of thrombosis in the setting of MPN; the effect that cytoreductive therapies and JAK inhibitors can have on markers of NETosis, and, finally, the novel therapeutic strategies targeting NETs to reduce the thrombotic complications in these patients.
Highlights
Philadelphia chromosome-negative chronic myeloproliferative neoplasms (MPN) i.e., polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), are clonal disorders of hematopoietic stem cells (HSC) that are characterized by a proliferation in the bone marrow (BM) of one or more myeloid lines
In the majority of studies included in this meta-analysis, the white blood cell (WBC) count was only measured at diagnosis or at the time of the enrollment, and overall thrombosis was evaluated without differentiating between arterial and venous events
The presence of neutrophil extracellular tramp has been documented in autoimmune diseases, diabetes, atherosclerosis, vasculitis, and cancer
Summary
Philadelphia chromosome-negative chronic myeloproliferative neoplasms (MPN) i.e., polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), are clonal disorders of hematopoietic stem cells (HSC) that are characterized by a proliferation in the bone marrow (BM) of one or more myeloid lines They share clinical features (e.g., splenomegaly, thrombotic complications, risk of leukemic transformation), and a common molecular basis: the dysregulation of the JAK-STAT pathway [1], which confers a hypersensitivity of HSC to the action of growth factors and cytokines, and, as a result, an overproduction of blood cells [2,3]. The complexity of the human MPN condition is amplified by co-operating mutations in myeloid genes that often accompany the p.V617F mutation in Janus Kinase 2gene (JAK2V617F) [6,7,8] Among this array of factors, a mounting body of clinical and biological evidence supports the role of leukocytes in the thrombosis of MPN patients. We will review the role of leukocytes, and neutrophils, in thrombotic complications associated with MPN
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