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Thromboinflammation is associated with high thrombotic risk in patients with newly diagnosed myeloproliferative neoplasms

Leukemia (2025)Cite this article

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Abstract

Thrombotic risk assessment is crucial in newly diagnosed essential thrombocythemia (ET) and polycythemia vera (PV) patients to guide cytoreductive therapy. We assessed whether thromboinflammation biomarkers would be good candidates to improve thrombosis risk stratification. We prospectively enrolled 394 newly diagnosed, cytoreductive therapy–naïve, ET and PV patients. We measured seven plasma biomarkers of neutrophil, monocyte, platelet, and endothelial activation, including NET markers, and evaluated their association with thrombosis risk scores at diagnosis. Multivariable analysis in the whole MPN cohort showed elevated calprotectin and tissue factor levels in high-risk versus low-risk patients using the conventional two-tiered score. This was also observed in ET patients only, but not in PV patients. Patients with a JAK2V617F allele burden >20% showed higher levels of three markers, including calprotectin, supporting its role in immunothrombosis. In PV patients, calprotectin correlated with the Venous Thrombosis Score (VETS), and five markers were elevated in those with prior venous thrombosis. Lastly, aspirin use was associated with lower H3Cit levels in patients with normal platelet counts, confirming its beneficial effect on NET formation. This is the largest study to date linking thromboinflammation markers to thrombotic risk in MPN patients and identifying potential biomarkers for future thrombosis risk scores.

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Fig. 1: Association of marker concentrations and clinical risk scores of thrombosis.
Fig. 2: Analysis of the impact of JAK2V617F mutation on marker concentrations.
Fig. 3: Analysis of marker concentrations and venous thrombosis score as history of thrombosis.
Fig. 4: Analysis of the impact of aspirin treatment on marker concentrations.

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Data availability

For original data, please contact chloe.james@inserm.fr.

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Acknowledgements

We thank the French group of MPN (France Intergroupe Syndrome Myéloproliferatifs, FIM) as the clinico-biological cohort FIMBANK team for the support in the conception and elaboration of the study, Fanny Robbesyn for the help in the coordination of the study, Valentin Landrieu for the help in calprotectin dosage realization, Audrey Bidet and the Center de Ressources Biologiques (CRB)- Cancer from Bordeaux hospital, all the CRBs involved in the preparation of samples.

Funding

This work was supported by grants from the association Force Hemato (“Appel à Projets Force Hemato”) and from the “Groupement Interrégional de Recherche Clinique et d’Innovation Sud-ouest Outre-Mer Hospitalier (GIRCI-SOHO)” (“Incitation à la recherche en cancérologie APIK 2018”). This work is a deliverable of the FIMBANK network, which was founded by the French ‘Institut National du Cancer’ (INCa BCB 2013 & 2020).

Author information

Authors and Affiliations

  1. Laboratory of Hematology, Bordeaux University Hospital, Bordeaux, France

    Alexandre Guy, Olivier Mansier, Sylvie Labrouche-Colomer & Chloe James

  2. Univ. Bordeaux, INSERM, BMC, U1034, Pessac, France

    Alexandre Guy, Olivier Mansier, Geoffrey Garcia, Sylvie Labrouche-Colomer, Marie-Lise Bats & Chloe James

  3. Department of Medical information, Bordeaux University Hospital, Bordeaux, France

    Matisse Decilap, Alexandre Catherineau & Rodolphe Thiébaut

  4. Laboratory of Biochemistry, Bordeaux University Hospital, Bordeaux, France

    Marie-Lise Bats

  5. Department of Clinical Hematology and Cellular Therapy, Angers University Hospital, Angers, France

    Françoise Boyer

  6. Department of Hematology and Clinical Hemostasis, Brest University Hospital, Brest, France

    Jean-Christophe Ianotto

  7. Laboratory of Hematology, Brest University Hospital, Brest, France

    Eric Lippert

  8. Department of Clinical Hematology and Cellular Therapy, APHP Henri Mondor University Hospital, Creteil, France

    Lydia Roy

  9. Paris Est Créteil University (UPEC), Paris, France

    Lydia Roy

  10. Department of Clinical Hematology, Oncopole Institute, Toulouse University Hospital, Toulouse, France

    Suzanne Tavitian

  11. Department of Clinical Hematology, Avignon Hospital Center, Avignon, France

    Borhane Slama & Borhane Slama

  12. Department of Clinical Hematology and Cellular Therapy, Limoges University Hospital, Limoges, France

    Stéphane Girault

  13. Department of Clinical Hematology, Bergonié Institute, Bordeaux, France

    Gabriel Etienne

  14. Department of Clinical Hematology, Annecy Hospital Center, Annecy, France

    Anne Parry

  15. Department of Clinical Hematology, Mont-De-Marsan Hospital Center, Mont-De-Marsan, France

    Arnaud Saint-Lezer

  16. Department of Internal Medicine and Hematology, Rochefort Hospital Center, Rochefort, France

    Guillaume Denis

  17. Department of Clinical Hematology and Cellular Therapy, Bordeaux University Hospital, Bordeaux, France

    Clémence Médiavilla

  18. Department of Internal Medicine, Bordeaux University Hospital, Bordeaux, France

    Jean-François Viallard

  19. Department of Clinical Hematology, APHP Paul Brousse Hospital, Villejuif, France

    Laurence Legros

  20. Department of Internal Medicine and Hematology, Nancy University Hospital, Nancy, France

    Dana Ranta

  21. Department of Clinical Hematology, Roubaix Hospital Center, Roubaix, France

    Mathieu Wemeau

  22. Department of Clinical Hematology, Léon Bérard Center, Lyon, France

    Franck-Emmanuel Nicolini

  23. Department of Internal Medicine, Dax Hospital Center, Dax, France

    François Lifermann

  24. Department of Clinical Hematology, Valenciennes Hospital Center, Valenciennes, France

    Nathalie Cambier

  25. Laboratory of Hematology, APHP Georges-Pompidou European Hospital, Paris, France

    Luc Darnige

  26. Laboratory of Hematology, Dijon University Hospital, Dijon, France

    François Girodon

  27. Clinical Investigations Center, APHP Saint-Louis Hospital, Paris, France

    Juliette Soret-Dulphy & Jean-Jacques Kiladjian

  28. Department of Clinical Hematology and Cellular Therapy, Poitiers University Hospital, Poitiers, France

    Émilie Cayssials

  29. Department of Clinical Hematology, Perpignan Hospital Center, Perpignan, France

    Fabienne Vacheret

  30. Univ Angers, Nantes Université, CHU Angers, Inserm, CNRS, CRCI2NA, F-49000, Angers, France

    Léa Sureau, Damien Luque Paz & Valérie Ugo

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  30. Émilie Cayssials
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  36. Rodolphe Thiébaut
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  37. Chloe James
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Consortia

on behalf of the French Intergroup of Myeloproliferative Neoplasms (FIM)

  • Alexandre Guy
  • , Olivier Mansier
  • , Matisse Decilap
  • , Alexandre Catherineau
  • , Geoffrey Garcia
  • , Sylvie Labrouche-Colomer
  • , Marie-Lise Bats
  • , Françoise Boyer
  • , Jean-Christophe Ianotto
  • , Eric Lippert
  • , Lydia Roy
  • , Suzanne Tavitian
  • , Borhane Slama
  • , Stéphane Girault
  • , Gabriel Etienne
  • , Anne Parry
  • , Arnaud Saint-Lezer
  • , Guillaume Denis
  • , Clémence Médiavilla
  • , Jean-François Viallard
  • , Laurence Legros
  • , Dana Ranta
  • , Mathieu Wemeau
  • , Franck-Emmanuel Nicolini
  • , François Lifermann
  • , Nathalie Cambier
  • , Luc Darnige
  • , François Girodon
  • , Juliette Soret-Dulphy
  • , Émilie Cayssials
  • , Fabienne Vacheret
  • , Léa Sureau
  • , Damien Luque Paz
  • , Valérie Ugo
  • , Jean-Jacques Kiladjian
  • , Rodolphe Thiébaut
  •  & Chloe James

Contributions

Contribution: CJ, AG and RT designed the study; MD, AC, RT, AG performed statistical analyses; GG, SLC, OM, MLB performed samples analysis; FB, J-C I, EL, LR, ST, BS, SG, GE, AP, A S-L, GD, CM, J-F V, LL, DR, MW, F-E N, FL, NC, LD, FG, J S-D, EC, FV, J-J K provided patients care and contributed to patients inclusion; LS, D L-P, VU coordinated data management of the FIMBANK biobank; AG and CJ wrote the manuscript; all authors provided data and approved the final manuscript.

Corresponding author

Correspondence to Chloe James.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

Informed consent was obtained from all study participants. The study was conducted in accordance with the principles of the Declaration of Helsinki. Approval was obtained from the Comité de Protection des Personnes (reference number: 19/060-3). All methods were performed in accordance with the relevant guidelines and regulations.

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Guy, A., Mansier, O., Decilap, M. et al. Thromboinflammation is associated with high thrombotic risk in patients with newly diagnosed myeloproliferative neoplasms. Leukemia (2025). https://doi.org/10.1038/s41375-025-02836-8

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