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Novel Pathophysiological Mechanisms of Thrombosis in Myeloproliferative Neoplasms

  • Myeloproliferative Neoplasms (B Stein, Section Editor)
  • Published:
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Abstract

Purpose of Review

Thrombosis remains a leading cause of morbidity and mortality in BCR/ABL negative myeloproliferative neoplasms (MPN). Circulating blood cells are both increased in quantity and qualitatively abnormal in MPN, resulting in an increased thrombotic risk. Herein, we review recently elucidated mechanisms of MPN thrombosis and discuss implications of drugs currently under investigation for MPN.

Recent Findings

Recent studies highlight that in JAK2V617F granulocytes and platelets, thrombo-inflammatory genes are upregulated. Furthermore, in JAK2V617F granulocytes, protein expression of integrin CD11b, tissue factor, and leukocyte alkaline phosphatase are all increased. Overall, myeloid cells, namely neutrophils, may contribute in several ways, such as through increased adhesion via β1 integrin binding to VCAM1, increased infiltration, and enhanced inducibility to extrude neutrophil extracellular traps. Non-myeloid inflammatory cells may also contribute via secretion of cytokines. With regard to red blood cells, number, rigidity, adhesion, and generation of microvesicles may lead to increased vascular resistance as well as increased cell-cell interactions that promote rolling and adhesion. Platelets may also contribute in a similar fashion. Lastly, the vasculature is also increasingly appreciated, as several studies have demonstrated increased endothelial expression of pro-coagulant and pro-adhesive proteins, such as von Willebrand factor or P-selectin in JAK2V617F endothelial cells.

Summary

With the advent of molecular diagnostics, MPN therapeutics are advancing beyond cytoreduction. Our increased understanding of pro-inflammatory and thrombotic pathophysiology in MPN provides a rational basis for evaluation of in-development MPN therapeutics to reduce thrombosis.

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Funding

Funding: Dr. Beckman received funding from Bayer and Novartis.

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Authors and Affiliations

  1. Department of Medicine, Division of Hematology and Oncology, University of North Carolina—Chapel Hill, Chapel Hill, NC, USA

    Brandi N. Reeves

  2. Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Brandi N. Reeves

  3. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Brandi N. Reeves

  4. Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA

    Joan D. Beckman

  5. Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, 420 Delaware St. SE, MMC 480, Minneapolis, MN, 55455, USA

    Joan D. Beckman

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Joan Beckman has received grants from Bayer and Novartis.

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Reeves, B.N., Beckman, J.D. Novel Pathophysiological Mechanisms of Thrombosis in Myeloproliferative Neoplasms. Curr Hematol Malig Rep 16, 304–313 (2021). https://doi.org/10.1007/s11899-021-00630-8

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