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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Inflammation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1365015

Elevated levels of damage-associated molecular patterns HMGB1 and S100A8/A9 coupled with Toll-like receptor-triggered monocyte activation fosters inflammation in patients with myelofibrosis

Provisionally accepted
Geraldine De Luca Geraldine De Luca 1,2Nora Goette Nora Goette 1Paola Lev Paola Lev 1,2Maria C. Baroni Pietto Maria C. Baroni Pietto 1,2Cecilia P. Marin Oyarzun Cecilia P. Marin Oyarzun 1,2,3Miguel A. Castro Rios Miguel A. Castro Rios 4Elena Beatriz Moiraghi Elena Beatriz Moiraghi 5Federico Sackmann Federico Sackmann 6Laureano J. Kamiya Laureano J. Kamiya 1,2Veronica Verri Veronica Verri 7Victoria Caula Victoria Caula 7Vanina Fernandez Vanina Fernandez 8Angeles Vicente Angeles Vicente 9Julio Pose Cabarcos Julio Pose Cabarcos 10Vanesa Caruso Vanesa Caruso 11Maria F. Camacho Maria F. Camacho 12Irene Larripa Irene Larripa 12Marina Khoury Marina Khoury 13Rosana F. Marta Rosana F. Marta 1,2Ana C. Glembotsky Ana C. Glembotsky 1,2Paula G. Heller Paula G. Heller 1,2*
  • 1 División Hematología Investigación, Instituto de Investigaciones Médicas Dr. Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina., CABA, Argentina
  • 2 Instituto de Investigaciones Médicas (IDIM), UBA-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina., CABA, Argentina
  • 3 INSERM, UMR 1287, Gustave Roussy, Université Paris Saclay, Villejuif France, Equipe labellisée Ligue Nationale contre le Cancer (current affiliation)., Villejuif, France
  • 4 Consultorios Hematológicos, Buenos Aires, Argentina., Buenos Aires, Buenos Aires, Argentina
  • 5 Hospital Ramos Mejía, Buenos Aires, Buenos Aires, Argentina
  • 6 Centro de Hematologia Pavlovsky, Fundaleu, Buenos Aires, Argentina., CABA, Argentina
  • 7 División Hematología Clínica, IDIM Dr. Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina., CABA, Argentina
  • 8 Hospital Posadas, Buenos Aires, Argentina, Buenos Aires, Argentina
  • 9 Hospital Alemán, Buenos Aires, Argentina, CABA, Argentina
  • 10 Sanatorio Otamendi Miroli, Buenos Aires, Argentina, CABA, Argentina
  • 11 Hospital General de Agudos Parmenio Piñero, Buenos Aires, Buenos Aires, Argentina
  • 12 Laboratorio de Genética Hematológica, Instituto de Medicina Experimental, IMEX-CONICET/Academia Nacional de Medicina, Buenos Aires, Argentina., CABA, Argentina
  • 13 Departamento de Docencia e Investigación, IDIM Dr. Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, CABA, Argentina

The final, formatted version of the article will be published soon.

    Inflammation plays a pivotal role in the pathogenesis of primary and post-essential thrombocythemia or post-polycythemia vera myelofibrosis (MF) in close cooperation with the underlying molecular drivers. This inflammatory state is induced by a dynamic spectrum of inflammatory cytokines, although recent evidence points to the participation of additional soluble inflammatory mediators. Damage-associated molecular patterns (DAMPs) represent endogenous signals released upon cell death or damage which trigger a potent innate immune response. We assessed the contribution of two prototypical DAMPs, HMGB1 and S100A8/A9, to MF inflammation. Circulating HMGB1 and S100A8/A9 were elevated in MF patients in parallel to the degree of systemic inflammation and levels increased progressively during advanced disease stages. Patients with elevated DAMPs had higher frequency of adverse clinical features, such as anemia, and inferior survival, suggesting their contribution to disease progression.

    Keywords: myelofibrosis, monocyte, Inflammation, damage-associated molecular patterns, HMGB1, S100A8/A9, Toll-Like Receptors

    Received: 03 Jan 2024; Accepted: 26 Aug 2024.

    Copyright: © 2024 De Luca, Goette, Lev, Baroni Pietto, Marin Oyarzun, Castro Rios, Moiraghi, Sackmann, Kamiya, Verri, Caula, Fernandez, Vicente, Pose Cabarcos, Caruso, Camacho, Larripa, Khoury, Marta, Glembotsky and Heller. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Paula G. Heller, División Hematología Investigación, Instituto de Investigaciones Médicas Dr. Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina., CABA, Argentina

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