title: Increased plasma nicotinamide phosphoribosyltransferase is associated with a hyperproliferative phenotype and restrains disease progression in MPN-associated myelofibrosis.
abstract: Myeloproliferative neoplasm (MPN)-associated myelofibrosis is a clonal, neoplastic disorder of the hematopoietic stem cells, in which inflammation and immune dysregulation play an important role. Extracellular nicotinamide phosphoribosyltransferase (eNAMPT), also known as visfatin, is a cytokine implicated in a number of inflammatory and neoplastic diseases. Here plasma levels of eNAMPT in patients with MPN-associated myelofibrosis and their effects on disease phenotype and outcomes were examined. The concordance of eNAMPT levels with the marker of general inflammation high-sensitivity C-reactive protein (hs-CRP) was also studied. A total of 333 MPN-associated myelofibrosis patients (187 males and 146 females) and 31 age- and gender-matched normal-weight healthy subjects were enrolled in the study main body. Levels of eNAMPT and hs-CRP were simultaneously assayed in 209 MPN-associated myelofibrosis patients. Twenty-four polycythemia vera or essential thrombocythemia patients were used as controls. eNAMPT was over expressed in MPN-associated myelofibrosis, and eNAMPT expression was correlated with higher white blood cell count, higher hemoglobin, and higher platelet count, suggesting that eNAMPT is an indispensable permissive agent for myeloproliferation of MPN-associated myelofibrosis. The lack of correlation between eNAMPT and hs-CRP revealed that eNAMPT in MPN-associated myelofibrosis does not behave as a canonical inflammatory cytokine. In addition, higher levels of eNAMPT predicted longer time to blast transformation, and protected against progression toward thrombocytopenia and large splenomegaly. In conclusion, in MPN-associated myelofibrosis high levels of eNAMPT mark the myeloproliferative potential and, at variance with a high number of cancers, are protective against disease progression. Am. J. Hematol. 91:709-713, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Center for the Study of Myelofibrosis. Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, 27100, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Rosti
authors.affiliation: Center for the Study of Myelofibrosis. Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, 27100, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Campanelli
authors.affiliation: Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, 27100, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Massa
authors.affiliation: Immunohematology and Transfusion Service, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Viarengo
authors.affiliation: Center for the Study of Myelofibrosis. Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, 27100, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Villani
authors.affiliation: Center for the Study of Myelofibrosis. Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, 27100, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Poletto
authors.affiliation: Center for the Study of Myelofibrosis. Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, 27100, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Bonetti
authors.affiliation: Center for the Study of Myelofibrosis. Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, 27100, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Catarsi
authors.affiliation: Center for the Study of Myelofibrosis. Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, 27100, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Magrini
authors.affiliation: Department of Pharmaceutical Sciences, Università Del Piemonte Orientale, Novara, Italy.
authors.forename: Ambra A
authors.initials: AA
authors.lastname: Grolla
authors.affiliation: Department of Pharmaceutical Sciences, Università Del Piemonte Orientale, Novara, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Travelli
authors.affiliation: Department of Pharmaceutical Sciences, Università Del Piemonte Orientale, Novara, Italy.
authors.forename: Armando A
authors.initials: AA
authors.lastname: Genazzani
authors.affiliation: Center for the Study of Myelofibrosis. Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, 27100, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Barosi
mesh_terms: D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D049109:Cell Proliferation; D016207:Cytokines / Q000097:blood*; D018450:Disease Progression; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D009196:Myeloproliferative Disorders / Q000473:pathology*; D054409:Nicotinamide Phosphoribosyltransferase / Q000097:blood*; D010641:Phenotype; D010976:Platelet Count; D011087:Polycythemia Vera; D055728:Primary Myelofibrosis / Q000473:pathology*; D011379:Prognosis; D013920:Thrombocythemia, Essential
chemical_list: D016207:Cytokines; D006454:Hemoglobins; D002097:C-Reactive Protein; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human