title: Driver mutations (JAK2V617F, MPLW515L/K or CALR), pentraxin-3 and C-reactive protein in essential thrombocythemia and polycythemia vera.
abstract: The driver mutations JAK2V617F, MPLW515L/K and CALR influence disease phenotype of myeloproliferative neoplasms (MPNs) and might sustain a condition of chronic inflammation. Pentraxin 3 (PTX3) and high-sensitivity C-reactive protein (hs-CRP) are inflammatory biomarkers potentially useful for refining prognostic classification of MPNs.
  
  
  
  We evaluated 305 with essential thrombocythemia (ET) and 172 polycythemia vera (PV) patients diagnosed according to the 2016 WHO criteria and with full molecular characterization for driver mutations.
  
  
  
  PTX3 levels were significantly increased in carriers of homozygous JAK2V617F mutation compared to all the other genotypes and triple negative ET patients, while hs-CRP levels were independent of the mutational profile. The risk of haematological evolution and death from any cause was about 2- and 1.5-fold increased in individuals with high PTX-3 levels, while the thrombosis rate tended to be lower. High hs-CRP levels were associated with risk of haematological evolution, death and also major thrombosis. After sequential adjustment for potential confounders (age, gender, diagnosis and treatments) and the presence of JAK2V617F homozygous status, high hs-CRP levels remained significant for all outcomes, while JAK2V617F homozygous status as well as treatments were the factors independently accounting for adverse outcomes among patients with high PTX3 levels.
  
  
  
  These results provide evidence that JAK2V617F mutation influences MPN-associated inflammation with a strong correlation between allele burden and PTX3 levels. Plasma levels of hs-CRP and PTX3 might be of prognostic value for patients with ET and PV, but their validation in future prospective studies is needed.
authors.affiliation: Hematology and Bone Marrow Transplant Unit, ASST Papa Giovanni XXIII Bergamo, Piazza OMS, 1, 24127, Bergamo, Italy. flussana@asst-pg23.it.
authors.forename: Federico
authors.identifier: 0000-0002-6510-8616
authors.initials: F
authors.lastname: Lussana
authors.affiliation: Research Foundation, ASST Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Carobbio
authors.affiliation: Hematology and Bone Marrow Transplant Unit, ASST Papa Giovanni XXIII Bergamo, Piazza OMS, 1, 24127, Bergamo, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Salmoiraghi
authors.affiliation: Department of Experimental and Clinical Medicine, CRIMM, Center Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Guglielmelli
authors.affiliation: Department of Experimental and Clinical Medicine, CRIMM, Center Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy.
authors.forename: Alessandro Maria
authors.initials: AM
authors.lastname: Vannucchi
authors.affiliation: Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bottazzi
authors.affiliation: Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Leone
authors.affiliation: Humanitas Clinical and Research Center, Rozzano, Milan, Italy.|Humanitas University, Rozzano, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.affiliation: Research Foundation, ASST Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Barbui
authors.affiliation: Hematology and Bone Marrow Transplant Unit, ASST Papa Giovanni XXIII Bergamo, Piazza OMS, 1, 24127, Bergamo, Italy.|Department of Oncology and Hematology, University of Milan, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000032:analysis / Q000235:genetics*; D037282:Calreticulin / Q000235:genetics*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics / Q000473:pathology; D009369:Neoplasms / Q000175:diagnosis; D011087:Polycythemia Vera / Q000235:genetics*; D011379:Prognosis; D000683:Serum Amyloid P-Component / Q000032:analysis / Q000235:genetics*; D013920:Thrombocythemia, Essential / Q000235:genetics*; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D037282:Calreticulin; D053614:Janus Kinase 2; D000683:Serum Amyloid P-Component; D000099153:Pentraxins
keywords: Essential thrombocythemia; Inflammation; Mutations; Polycythemia vera