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Myeloproliferative neoplasms and inflammation: whether to target the malignant clone or the inflammatory process or both

Leukemia volume 30, pages 1018–1024 (2016)Cite this article

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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.

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Acknowledgements

This study summarizes the results of discussions and deliberations during a series of interactive working sessions organized by the European LeukemiaNet MPN group between June 2014 and February 2015. We thank Professors Radek Skoda, Sylvie Hermouet, Vladan Čokić, Dominik Wolf, Hans-Michael Kvasnicka, Jerry Spivak and Martin Griesshammer for participating in some of the ELN MPN group workshops and for their helpful suggestions, and the Alpine Oncology Foundation (AOF) team, in particular Dr Alpa Parmar, for arranging the workshops. AOF acknowledges receiving unrestricted educational research support from Novartis Oncology.

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Authors and Affiliations

  1. Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany

    S Koschmieder

  2. Division of Hematology/Oncology, Tufts University Medical Center, Boston, MA, USA

    T I Mughal

  3. Department of Hematology, Roskilde Hospital, Copenhagen University Hospital, Roskilde, Denmark

    H C Hasselbalch

  4. Center for the Study and Treatment of Myelofibrosis, Biotechnology Research Laboratories, Fondazione IRCCS ‘Policlinico San Matteo’, Pavia, Italy

    G Barosi

  5. Department of Internal Medicine I, Division of Hematology and Hemostaseology, and Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria

    P Valent

  6. Clinical Investigations Center (INSERM CIC 1427), Hôpital Saint-Louis and Paris Diderot University, Paris, France

    J-J Kiladjian

  7. Division of Hematology and Blood Coagulation, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria

    G Jeryczynski & H Gisslinger

  8. Division of Molecular Hematology, University Hospital Freiburg, Center for Clinical Research, Freiburg, Germany

    J S Jutzi & H L Pahl

  9. Spemann Graduate School of Biology and Medicine (SGBM) and Faculty of Biology, University of Freiburg, Freiburg, Germany

    J S Jutzi

  10. Universitätsmedizin Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany

    R Hehlmann

  11. Dipartimento di Medicina Sperimentale e Clinica, CRIMM, Centro di Ricerca e Innovazione e Laboratorio Congiunto per le Malattie Mieloproliferative, Centro Denothe, Azienda Ospedaliera Universitaria Careggi, Università degli Studi, Firenze, Italy

    A Maria Vannucchi

  12. Department of Hematology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain

    F Cervantes

  13. Division of Hematology-Oncology, Myeloproliferative Neoplasm Center, Weill Cornell Medical College, New York, NY, USA

    R T Silver

  14. Clinical Research Center and Hematology, Ospedale Papa Giovanni XXIII, Bergamo, Italy

    T Barbui

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Correspondence to S Koschmieder.

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Competing interests

Steffen Koschmieder: research funding (Novartis and Novartis Foundation); consultancy and advisory boards (Ariad, AOP, Baxalta, Bristol-Myers Squibb, CTI, Novartis, Pfizer, Sanofi); honoraria and travel grants (Ariad, Alexion, AOP, Baxalta, Bristol-Myers Squibb, Celgene, CTI, Novartis, Pfizer, Sanofi, Shire). Hans C Hasselbalch: research grant (Novartis). Peter Valent: honoraria (Novartis, Ariad, Pfizer und BMS); grant support (Novartis, Ariad); consultancy (Novartis Global PKC412 Trial). Heike Pahl: consultancy and advisory boards (AOP, Baxalta, Novartis, Shire). Rüdiger Hehlmann: research funding (BMS and Novartis). Alessandro Vannucchi: honoraria for advisory board and speaker fees (Novartis). Francisco Cervantes: advisory board (Novartis, AOP, and CTI-Baxter); speakers bureau (Novartis and CTI-Baxter).

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Koschmieder, S., Mughal, T., Hasselbalch, H. et al. Myeloproliferative neoplasms and inflammation: whether to target the malignant clone or the inflammatory process or both. Leukemia 30, 1018–1024 (2016). https://doi.org/10.1038/leu.2016.12

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