title: Myeloproliferative neoplasms and inflammation: whether to target the malignant clone or the inflammatory process or both.
abstract: The Philadelphia-negative myeloproliferative neoplasms (MPNs) are clonal disorders involving hematopoietic stem and progenitor cells and are associated with myeloproliferation, splenomegaly and constitutional symptoms. Similar signs and symptoms can also be found in patients with chronic inflammatory diseases, and inflammatory processes have been found to play an important role in the pathogenesis and progression of MPNs. Signal transduction pathways involving JAK1, JAK2, STAT3 and STAT5 are causally involved in driving both the malignant cells and the inflammatory process. Moreover, anti-inflammatory and immune-modulating drugs have been used successfully in the treatment of MPNs. However, to date, many unresoved issues remain. These include the role of somatic mutations that are present in addition to JAK2V617F, CALR and MPL W515 mutations, the interdependency of malignant and nonmalignant cells and the means to eradicate MPN-initiating and -maintaining cells. It is imperative for successful therapeutic approaches to define whether the malignant clone or the inflammatory cells or both should be targeted. The present review will cover three aspects of the role of inflammation in MPNs: inflammatory states as important differential diagnoses in cases of suspected MPN (that is, in the absence of a clonal marker), the role of inflammation in MPN pathogenesis and progression and the use of anti-inflammatory drugs for MPNs. The findings emphasize the need to separate the inflammatory processes from the malignancy in order to improve our understanding of the pathogenesis, diagnosis and treatment of patients with Philadelphia-negative MPNs.
authors: Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.
authors: S
authors: S
authors: Koschmieder
authors: Division of Hematology/Oncology, Tufts University Medical Center, Boston, MA, USA.
authors: T I
authors: TI
authors: Mughal
authors: Department of Hematology, Roskilde Hospital, Copenhagen University Hospital, Roskilde, Denmark.
authors: H C
authors: HC
authors: Hasselbalch
authors: Center for the Study and Treatment of Myelofibrosis, Biotechnology Research Laboratories, Fondazione IRCCS 'Policlinico San Matteo', Pavia, Italy.
authors: G
authors: G
authors: Barosi
authors: Department of Internal Medicine I, Division of Hematology and Hemostaseology, and Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.
authors: P
authors: P
authors: Valent
authors: Clinical Investigations Center (INSERM CIC 1427), Hôpital Saint-Louis and Paris Diderot University, Paris, France.
authors: J-J
authors: JJ
authors: Kiladjian
authors: Division of Hematology and Blood Coagulation, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
authors: G
authors: G
authors: Jeryczynski
authors: Division of Hematology and Blood Coagulation, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
authors: H
authors: H
authors: Gisslinger
authors: Division of Molecular Hematology, University Hospital Freiburg, Center for Clinical Research, Freiburg, Germany.|Spemann Graduate School of Biology and Medicine (SGBM) and Faculty of Biology, University of Freiburg, Freiburg, Germany.
authors: J S
authors: JS
authors: Jutzi
authors: Division of Molecular Hematology, University Hospital Freiburg, Center for Clinical Research, Freiburg, Germany.
authors: H L
authors: HL
authors: Pahl
authors: Universitätsmedizin Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.
authors: R
authors: R
authors: Hehlmann
authors: CRIMM, Centro di Ricerca e Innovazione e Laboratorio Congiunto per le Malattie Mieloproliferative, Dipartimento di Medicina Sperimentale e Clinica, Centro Denothe, Azienda Ospedaliera Universitaria Careggi, Università degli Studi, Firenze, Italy.
authors: A
authors: A
authors: Maria Vannucchi
authors: Department of Hematology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors: F
authors: F
authors: Cervantes
authors: Myeloproliferative Neoplasm Center, Division of Hematology-Oncology, Weill Cornell Medical College, New York, NY, USA.
authors: R T
authors: RT
authors: Silver
authors: Clinical Research Center and Hematology, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors: T
authors: T
authors: Barbui
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002999:Clone Cells / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D009196:Myeloproliferative Disorders / Q000188:drug therapy* / Q000473:pathology; D009369:Neoplasms / Q000473:pathology*
chemical_list: D000893:Anti-Inflammatory Agents