NETosis implications in the pathogenesis of Myeloproliferative Neoplasia (MPN)

NETosis is a regulated cell death mechanism mediated by Neutrophil extracellular traps (NETs) from neutrophils and is distinct from other cell death mechanisms, including necrosis and apoptosis. One of the hallmarks of NETosis is the extrusion of decompacted DNA strands along with a membrane rupture in several myeloid cell lines, such as neutrophils, eosinophils, mast cells, and macrophages. In neutrophilic stimulation, decondensed DNA with a complex of histones and other granular proteins are created in NETs. NETosis is occurred in infections, autoimmune disorders, sepses, and myeloproliferative disorders. Although the structure has the ability to trap microorganisms, it contributes to autoimmune pathogenesis and thrombosis. NETosis has commonly been accompanied with interferon-inflammatory responses and may lead to exacerbation of autoimmune diseases, preliminarily due to providing self-antigens and co-stimulation signals.Recently, studies have shown that cancer induces a systematic environment that triggers neutrophils by releasing NETs. The results showed that peripheral blood of rats with leukemic and tumor-bearing mice is more susceptible to the formation of NETs in the ex vivio environment. In patients with Myeloproliferative Neoplasia (MPN), NETosis has been indicated to induce thrombosis. Myeloproliferative leukemia patients harboring JAK2V617F mutation have significantly increased construction rate of NETs, while patients receiving JAK1/2 inhibitors have decreased formation rate. It seems that early diagnosis of NETosis with molecular techniques in cancer patients prevents the formation of thrombosis and, subsequent, complications.

Keywords:

Neutrophil extracellular traps , NETosis , Myeloproliferative Neoplasia , Neutrophil , Cancer