title: Neutrophil extracellular trap formation and circulating nucleosomes in patients with chronic myeloproliferative neoplasms.
abstract: The mechanisms underlying increased thrombotic risk in chronic myeloproliferative neoplasms (MPN) are incompletely understood. We assessed whether neutrophil extracellular traps (NETs), which promote thrombosis, contribute to the procoagulant state in essential thrombocythemia, polycythemia vera and myelofibrosis (MF) patients. Although MPN neutrophils showed increased basal reactive oxygen species (ROS), enhanced NETosis by unstimulated neutrophils was an infrequent finding, whereas PMA-triggered NETosis was impaired, particularly in MF, due to decreased PMA-triggered ROS production. Elevated circulating nucleosomes were a prominent finding and were higher in patients with advanced disease, which may have potential prognostic implication. Histone-MPO complexes, proposed as specific NET biomarker, were seldomly detected, suggesting NETs may not be the main source of nucleosomes in most patients, whereas their correlation with high LDH points to increased cell turn-over as a plausible origin. Lack of association of nucleosomes or NETs with thrombosis or activation markers does not support their use as predictors of thrombosis although prospective studies in a larger cohort may help define their potential contribution to MPN thrombosis. These results do not provide evidence for relevant in vivo NETosis in MPN patients under steady state conditions, although availability of standardized NET biomarkers may contribute to further research in this field.
authors.affiliation: Department of Hematology Research, Institute of Medical Research "Alfredo Lanari", University of Buenos Aires, National Council for Scientific and Technological Research (CONICET), Buenos Aires, Argentina.
authors.forename: Cecilia P
authors.initials: CP
authors.lastname: Marin Oyarzún
authors.affiliation: Laboratory of Experimental Thrombosis, Institute of Experimental Medicine (IMEX)- CONICET, National Academy of Medicine, Buenos Aires, Argentina.
authors.forename: Agostina
authors.initials: A
authors.lastname: Carestia
authors.affiliation: Department of Hematology Research, Institute of Medical Research "Alfredo Lanari", University of Buenos Aires, National Council for Scientific and Technological Research (CONICET), Buenos Aires, Argentina.
authors.forename: Paola R
authors.initials: PR
authors.lastname: Lev
authors.affiliation: Department of Hematology Research, Institute of Medical Research "Alfredo Lanari", University of Buenos Aires, National Council for Scientific and Technological Research (CONICET), Buenos Aires, Argentina.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Glembotsky
authors.affiliation: Consultorios Hematológicos, Buenos Aires, Argentina.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Castro Ríos
authors.affiliation: Department of Hematology, Hospital Ramos Mejía, Buenos Aires, Argentina.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Moiraghi
authors.affiliation: Department of Hematology Research, Institute of Medical Research "Alfredo Lanari", University of Buenos Aires, National Council for Scientific and Technological Research (CONICET), Buenos Aires, Argentina.
authors.forename: Felisa C
authors.initials: FC
authors.lastname: Molinas
authors.affiliation: Department of Hematology Research, Institute of Medical Research "Alfredo Lanari", University of Buenos Aires, National Council for Scientific and Technological Research (CONICET), Buenos Aires, Argentina.
authors.forename: Rosana F
authors.initials: RF
authors.lastname: Marta
authors.affiliation: Laboratory of Experimental Thrombosis, Institute of Experimental Medicine (IMEX)- CONICET, National Academy of Medicine, Buenos Aires, Argentina.
authors.forename: Mirta
authors.initials: M
authors.lastname: Schattner
authors.affiliation: Department of Hematology Research, Institute of Medical Research "Alfredo Lanari", University of Buenos Aires, National Council for Scientific and Technological Research (CONICET), Buenos Aires, Argentina.
authors.forename: Paula G
authors.initials: PG
authors.lastname: Heller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D002908:Chronic Disease; D065206:Extracellular Traps / Q000378:metabolism*; D005260:Female; D019337:Hematologic Neoplasms / Q000097:blood* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000097:blood* / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D009707:Nucleosomes / Q000378:metabolism*; D009195:Peroxidase / Q000097:blood; D017382:Reactive Oxygen Species / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D009707:Nucleosomes; D017382:Reactive Oxygen Species; D009195:Peroxidase