title: Pathogenesis of Myeloproliferative Neoplasms: Role and Mechanisms of Chronic Inflammation.
abstract: Myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal diseases characterized by the excessive and chronic production of mature cells from one or several of the myeloid lineages. Recent advances in the biology of MPNs have greatly facilitated their molecular diagnosis since most patients present with mutation(s) in the JAK2, MPL, or CALR genes. Yet the roles played by these mutations in the pathogenesis and main complications of the different subtypes of MPNs are not fully elucidated. Importantly, chronic inflammation has long been associated with MPN disease and some of the symptoms and complications can be linked to inflammation. Moreover, the JAK inhibitor clinical trials showed that the reduction of symptoms linked to inflammation was beneficial to patients even in the absence of significant decrease in the JAK2-V617F mutant load. These observations suggested that part of the inflammation observed in patients with JAK2-mutated MPNs may not be the consequence of JAK2 mutation. The aim of this paper is to review the different aspects of inflammation in MPNs, the molecular mechanisms involved, the role of specific genetic defects, and the evidence that increased production of certain cytokines depends or not on MPN-associated mutations, and to discuss possible nongenetic causes of inflammation.
authors.affiliation: Inserm UMR 892, CNRS UMR 6299, Centre de Recherche en Cancérologie Nantes-Angers, Institut de Recherche en Santé, Université de Nantes, 44007 Nantes, France ; Laboratoire d'Hématologie, Centre Hospitalier Universitaire de Nantes, 44093 Nantes Cedex, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Hermouet
authors.affiliation: Inserm UMR 892, CNRS UMR 6299, Centre de Recherche en Cancérologie Nantes-Angers, Institut de Recherche en Santé, Université de Nantes, 44007 Nantes, France ; Laboratoire de Biochimie, Centre Hospitalier Universitaire de Nantes, 44093 Nantes Cedex, France.
authors.forename: Edith
authors.initials: E
authors.lastname: Bigot-Corbel
authors.affiliation: Inserm UMR 892, CNRS UMR 6299, Centre de Recherche en Cancérologie Nantes-Angers, Institut de Recherche en Santé, Université de Nantes, 44007 Nantes, France ; Ecole Pratique des Hautes Etudes, Laboratoire de Génétique Oncologique, 44007 Nantes, France.
authors.forename: Betty
authors.initials: B
authors.lastname: Gardie
mesh_terms: D037282:Calreticulin / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000235:genetics / Q000503:physiopathology; D007249:Inflammation / Q000235:genetics / Q000503:physiopathology*; D053614:Janus Kinase 2 / Q000235:genetics; D007938:Leukemia; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000503:physiopathology; D008415:Mastocytosis / Q000235:genetics / Q000503:physiopathology; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics / Q000503:physiopathology*; D009369:Neoplasms / Q000503:physiopathology*; D010641:Phenotype; D011087:Polycythemia Vera / Q000235:genetics / Q000503:physiopathology; D055728:Primary Myelofibrosis / Q000235:genetics / Q000503:physiopathology; D053628:Receptors, Thrombopoietin / Q000235:genetics; D013920:Thrombocythemia, Essential / Q000235:genetics / Q000503:physiopathology
chemical_list: C576483:CALR protein, human; D037282:Calreticulin; D016207:Cytokines; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2