The Role of Leukocytes in the Formation of Neutrophil Extracellular Traps and Thrombosis in Ph-Negative Myeloproliferative Neoplasms: A Literature Review

BT Dzhumabaeva

National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Boldukyz Tolgonbaevna Dzhumabaeva, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-64-63, +7(926)271-92-82; e-mail: bola.blood@yandex.ru

For citation: Dzhumabaeva BT. The Role of Leukocytes in the Formation of Neutrophil Extracellular Traps and Thrombosis in Ph-Negative Myeloproliferative Neoplasms: A Literature Review. Clinical oncohematology. 2023;16(3):263–7. (In Russ).

DOI: 10.21320/2500-2139-2023-16-3-263-267


ABSTRACT

Thrombotic complications often cause death in patients with chronic Ph-negative myeloproliferative neoplasms (MPNs). In spite of numerous studies, the pathogenesis of thrombus formation in MPN patients remains unclear. Its mechanism is complex and is determined by many factors. One of the essential phases in thrombogenesis is characterized by the activation of cell mechanisms and formation of neutrophil extracellular traps (NETs). NETs consist of DNA strands, histones, granular proteins and along with pathogen destruction provide an ideal matrix for platelet and clotting mechanism activation.

Keywords: myeloproliferative neoplasms, neutrophils, thrombosis, neutrophil extracellular traps (NETs).

Received: December 14, 2022

Accepted: May 29, 2023

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REFERENCES

  1. Rumi E, Cazzola M. Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms. 2017;129(6):680–92. doi: 10.1182/blood-2016-10-695957.
  2. Falanga A, Marchetti M. Thrombosis in Myeloproliferative Neoplasms. Semin Thromb Hemost. 2014;40(3):348–58. doi:1055/s-0034-1370794.
  3. Barbui T, Finazzi G, Falanga, A. Myeloproliferative neoplasms and thrombosis. Blood. 2013;122(13):2176–84. doi: 1182/blood-2013-03-460154.
  4. Artoni A, Bucciarelli P, Martinelli I. Cerebral thrombosis and myeloproliferative neoplasms. Curr Neurol Neurosci Rep. 2014;14(11):496. doi:1007/s11910-014-0496-y.
  5. Kaifie A, Kirschner M, Wolf D, et al. Study Alliance Leukemia (SAL). Bleeding, thrombosis, and anticoagulation in myeloproliferative neoplasms (MPN): analysis from the German SAL-MPN-registry. J Hematol Oncol. 2016;9(1):18. doi: 10.1186/s13045-016-0242-9.
  6. Hultcrantz M, Bjorkholm M, Dickman PW, et al. Risk for arterial and venous thrombosis in patients with myeloproliferative neoplasms: A population-based cohort study. Ann Intern Med. 2018;168(5):317–25. doi:7326/M17-0028.
  7. Smalberg JH, Arends LR, Valla DC, et al. Myeloproliferative neoplasms in Budd-Chiari syndrome and portal vein thrombosis: a meta-analysis. Blood. 2012;120(25):4921–8. doi: 10.1182/blood-2011-09-376517.
  8. Gangat N, Wolanskyj AP, Schwager SM, et al. Leukocytosis at diagnosis and the risk of subsequent thrombosis in patients with low-risk essential thrombocythemia and polycythemia vera. 2009;115(24):5740–5. doi: 10.1002/cncr.24664
  9. Tefferi A, Gangat N, Wolanskyj A. The interaction between leukocytosis and other risk factors for thrombosis in essential thrombocythemia. Blood. 2007;109(9): doi: 10.1182/blood-2007-01-066985.
  10. Marin Oyarzun C.P, Heller P.G. Platelets as mediators of thromboinflammation in chronic myeloproliferative neoplasms. Front Immunol. 2019;10: doi: 10.3389/fimmu.2019.01373.
  11. Ferrer-Marin F, Cuenca-Zamora EJ, Guijarro-Carrillo PJ, Teruel-Montoya R. Emerging Role of Neutrophils in the Thrombosis of Chronic Myeloproliferative Neoplasms. Int J Mol Sci. 2021;22(3):1143. doi: 10.3390/ijms22031143.
  12. Landolfi R, Di Gennaro L, Barbui T, et al. Leukocytosis as a major thrombotic risk factor in patients with polycythemia vera. 2007;109(6):2446–52. doi: 10.1182/blood-2006-08-042515.
  13. Tefferi A, Pardanani A. Myeloproliferative neoplasms: A contemporary review. JAMA Oncol. 2015;1(1):97–105. doi: 1001/jamaoncol.2015.89.
  14. Carobbio A, Ferrari A, Masciulli A, et al. Leukocytosis and thrombosis in essential thrombocythemia and polycythemia vera: A systematic review and meta-analysis. Blood Adv. 2019;3(11):1729–37. doi: 10.1182/bloodadvances.
  15. Barbui T, Carobbio A, Rambaldi A, Finazzi G. Perspectives on thrombosis in essential thrombocythemia and polycythemia vera: Is leukocytosis a causative factor? 2009;114(4):759–63. doi: 10.1182/blood-2009-02-206797.
  16. Campbell PJ, MacLean C, Beer PA, et al. Correlation of blood counts with vascular complications in essential thrombocythemia: Analysis of the prospective PT1 cohort. 2012;120(7):1409–11. doi: 10.1182/blood-2012-04-424911.
  17. Carobbio A, Thiele J, Passamonti F, et al. Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: An international study of 891 patients. 2011;117(22):5857–9. doi: 10.1182/blood-2011-02-339002.
  18. Repsold L, Joubert AM. Platelet Function, Role in Thrombosis, Inflammation, and Consequences in Chronic Myeloproliferative Disorders. Cells. 2021;10(11):3034. doi: 10.3390/cells10113034.
  19. Nangalia J, Green AR. Myeloproliferative neoplasms: From origins to outcomes. Hematology Am Soc Hematol Educ Program. 2017;2017(1):470–9. doi: 10.1182/asheducation-2017.1.470.
  20. Wolach O, Sellar RS, Martinod K, et al. Increased neutrophil extracellular trap formation promotes thrombosis in myeloproliferative neoplasms. Sci Transl Med. 2018;10(436):eaan8292. doi: 10.1126/scitranslmed.aan8292.
  21. Wilkins BS. Myeloproliferative neoplasms. Diagn Histopathol. 2021;27(9):373–9.
  22. Harrison CN, Lee JS. Myeloproliferative neoplasms. 2017;45:275–9.
  23. Edelmann B, Gupta N, Schnoeder TM, et al. JAK2-V617F promotes venous thrombosis through β1/β2 integrin activation. J Clin Invest. 2018;128(10):4359–71. doi: 10.1172/JCI90312.
  24. Falanga A, Marchetti M, Barbui T, Smith CW. Pathogenesis of Thrombosis in Essential Thrombocythemia and Polycythemia Vera: The Role of Neutrophils. Semin Hematol. 2005;42(4):239–47. doi: 10.1053/j.seminhematol.2005.05.023.
  25. Gupta N, Edelmann B, Schnoeder TM, et al. JAK2-V617F activates β1-integrin-mediated adhesion of granulocytes to vascular cell adhesion molecule 1. 2017;31(5):1223–6. doi: 10.1038/leu.2017.26.
  26. Lisman T. Platelet–neutrophil interactions as drivers of inflammatory and thrombotic disease. Cell Tissue Res. 2018;37(3):567–76. doi: 10.1007/s00441-017-2727-4.
  27. Arellano-Rodrigo E, Alvarez-Larran A, Reverter JC, et al. Increased platelet and leukocyte activation as contributing mechanisms for thrombosis in essential thrombocythemia and correlation with the JAK2 mutational status. 2006;91(2):169–75.
  28. Li, P, Li M, Lindberg MR, et al. PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. J Exp Med. 2010;207(9):1853–62. doi:1084/jem.20100239.
  29. Leshner M, Wang S, Lewis C, et al. PAD4 mediated histone hypercitrullination induces heterochromatin decondensation and chromatin unfolding to form neutrophil extracellular trap-like structures. Front Immunol. 2012;3:307. doi:3389/fimmu.2012.00307.
  30. Thalin S, Hisada Y, Lundstrom S, et al. Neutrophil Extracellular Traps: Villains and Targets in Arterial, Venous, and Cancer-Associated Thrombosis Review. Arterioscler Thromb Vasc Biol. 2019;39(9):1724–38. doi: 10.1161/ATVBAHA.119.312463.
  31. Jorch SK, Kubes P. An emerging role for neutrophil extracellular traps in noninfectious disease. Nat Med. 2017;23(3):279–87. doi:1038/nm.4294.
  32. Desai J, Mulay SR, Nakazawa D, Anders HJ. Matters of life and death. How neutrophils die or survive along NET release and is “NETosis” = necroptosis? Cell Mol Life Sci. 2016;73(11–12):2211–9. doi:1007/s00018-016-2195-0.
  33. Von Bruhl ML, Stark K, Steinhart A, et al. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med. 2012;209(4):819–35. doi:1084/jem.20112322.
  34. Massberg S, Grahl L, von Bruehl M-L, et al. Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat Med. 2010;16(8):887–96. doi:1038/nm.2184.
  35. Fuchs TA, Brill A, Duerschmied D, et al. Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci USA. 2010;107(36):15880–5. doi: 10.1073/pnas.1005743107.
  36. Steppich BA, Seitz I, Busch G, et al. Modulation of tissue factor and tissue factor pathway inhibitor-1 by neutrophil proteases. Thromb Haemost. 2008;100(6):1068–75.
  37. Jorda RE, Nelson RM, Kilpatrick J, et al. Inactivation of human antithrombin by neutrophil elastase. Kinetics of the heparin-dependent reaction. J Biol Chem. 1989;264(18):10493–500.
  38. Kambas K, Mitroulis I, Ritis K. The emerging role of neutrophils in thrombosis—the journey of TF through NETs. Front Immunol. 2012;3:385. doi:3389/fimmu.2012.00385.
  39. Schmidt S, Daniliants D, Hiller E, et al. Increased levels of NETosis in myeloproliferative neoplasms are not linked to thrombotic events. Blood Adv. 2021;5(18):3515–27. doi: 10.1182/bloodadvances.2020004061.