INCREASED CIRCULATING PLATELET-NEUTROPHIL COMPLEXES IN ADULT NEWLY DIAGNOSED NON-HODGKINS‘S LYMPHOMA PATIENTS

Authors

  • Sheniz Yuzeir Clinic of Hematology, Medical University in Varna, Bulgaria
  • Bozhidara Shtereva Department of Medical Genetics, Medical University in Varna, Bulgaria
  • Liana Gercheva Clinic of Hematology, Acibadem City Clinic Tokuda Hospital in Sofia, Bulgaria

Keywords:

platelet-neutrophil complexes, aggressive and indolent Non-Hodgkin's lymphoma

Abstract

Non-Hodgkin’s lymphoma (NHL) is a group of lymphoproliferative malignant disorders with heterogeneous histological, biological and clinical characteristics. Non-Hodgkin’s lymphoma is characterized by  clonal abnormal proliferation and/or accumulation of B or T lymphocytes. Platelets and neutrophils interact during infection, inflammation and thrombosis and modulate each other’s functions.The formation of complexes between neutrophils and circulating platelets (platelet-neutrophil complexes - PNC) is a fundamental mechanism that is known but poorly studied in non-Hodgkin's lymphomas. Aims: We aimed to investigate the serum level of circulating platelet-neutrophil complexes in newly diagnosed non-Hodgkin's lymphoma (NHL) patients and their relationship with clinicopathological characteristics and prognostic parameters. Material and methods: A total  88 patients with  pathologically verified NHL and 20 healthy controls were analyzed. 34 were  with Diffuse large B-cell lymphoma (DLBCL), 9 with Mantel cell lymphoma( MCL), 4  with Peripheral T-cell lymphoma (PTCL), 15 with Marginal zone lymphoma (MZL), 10 with Follicular lymphoma( FL), 1 patient with Plasmoablastic  lymphoma(PBL), 1 with Lymphoplasmacytic Lymphoma (LPL) and 14 with Small lymphocytic lymphoma (SLL). Serum levels of PNC were measured by flow cytometric analysis of peripheral blood. The results were statistically analyzed by dispersion, comparison and regression methods.

Results: PNC levels were significantly higher in patients with NHL compared to healthy controls (p<0.01).  PNC levels were significantly higher in the  group of patients with aggressive NHL compared with the group of patients with inolent NHL (respectively p= 0.05).  There was a strong significant correlation between PNC and Platelett (р=0.032), PNC and Absolute Neutrophil Count (ANC) (р=0.015) and PNC and Hemoglobin  (r = 0.463; p < 0.001). No correlation was found with leukocyte count, LDH, B symptoms, β2-микроглобулин and absolute lymphocyte count (ALC ).                                                                                                            Conclusions:  Elevated levels of PNC are associated with increased tumor growth and could be an independent negative prognostic factor in development of NHL.

References

Arachiche, A., Mumaw, M. M., de la Fuente, M., & Nieman, M. T. (2013). Protease-activated receptor 1 (PAR1) and PAR4 heterodimers are required for PAR1-enhanced cleavage of PAR4 by α-thrombin. J Biol Chem. 288(45): p. 32553-32562

Celi, A., Pellegrini, G., Lorenzet, R. et al. (1994). P-Selectin Induces the Expression of Tissue Factor on Monocytes. PNAS.;91:8767–8771.

Coughlin, S.R. (2005). Protease-activated receptors in hemostasis, thrombosis and vascular biology. J Thromb Haemost. 3: p. 1800-1814

Chen, H., & Kahn, M. L. (2003). Reciprocal Signaling by Integrin and Nonintegrin Receptors during Collagen Activation of Platelets. Mol Cell Biol. 23(14): p. 4764-4777.

Claire, K. M., Adam, J. M., Cara, M. B., Joseph, A. J., Nabila, A., Priyanka, G., Erin, L. C., Clare, A. K., Tess, Z. G., Leah, M. W., James, C. W., Randall, G. W., (2020). Platelet-T cell aggregates in lung cancer patients: Implications for thrombosis PLoS One. 2020 Aug 10;15(8):e0236966. doi: 10.1371/journal.pone.0236966

Evans, L.S., & Hancock, B.W. (2003). Non-Hodgkin lymphoma, Lanceт362(9378):139-46. doi: 10.1016/S0140-6736(03)13868-8

Etulain, J., Martinod, K., Wong, S.L., Cifuni, S.M., Schattner, M., & Wagner, D.D. (2015). P-selectin promotes neutrophil extracellular trap formation in mice. Blood 126:242–6. doi:10.1182/blood-2015-01-624023

Falanga, A., Marchetti, M., vangelista, V., Vignoli, A., Cicini, M., Balicco, M. et al (2000). Polymorphonuclear leukocyte activation and hemostasis in patients with essential thrombocythemia and polycythemia vera, Blood.;96:4261-6.

Furman, M.I., Barnard, M.R., Krueger, L.A. et al. (2001). Circulating monocyte- platelet аggregates are an early marker of acute myocardial infarction. JAm Coll Cardiol. 38:1002–1006.

Gawaz, M., Fateh-Moghadam, S., Pilz, G., et al.(1995). Platelet activation and interaction with leucocytes in patients with sepsis or multiple organ failure. Eur J Clin Invest ;25:843–851.

Jin, J., Daniel, J. L., & Kunapuli S. P. (1998). Molecular Basis for ADP-induced Platelet Activation. J Biol Chem,. 273: p. 2030-2034

Joseph, J.E., Harrison, P., Mackie, J.M., et al (2001). Increased circulating Platelet –leucocyte complexes and platelet activation in patients with antiphospholipid syndrome, systemic lupus erythematosus and rheumatoid arthritis.Br J Haematol.;115:451–459

Kaplar, M., Kappelmayer, J., Kiss, A., et al. (2000). Increased leukocyte-platelet adhesion in chronic myeloproliferative disorders with high platelet counts.Platelets. 11:183–184.

Kasirer-Friede, A., Kahn, M. L., & Shattil, S. J (2007). Platelet integrins and immunoreceptors. Immunological Reviews,. 218: p. 247-264

Kauffenstein, G., Bergmeier, W., Eckly, A., Ohlmann, P., Léon, C., Cazanave, J. P., Nieswandt, B., Gachet, C (2001). The P2Y(12) receptor induces platelet aggregation through weak activation of the alpha(IIb)beta(3) integrin--a phosphoinositide 3-kinase-dependent mechanism. FEBS Lett,. 505(2): p. 281-290.

Khan, A., Li, D., Ibrahim, S., Smyth, E., & Woulfe, D. S. (2014). The physical association of the P2Y12 receptor with PAR4 regulates arrestin-mediated Akt activation. Mol Pharmacol, 86(1): p. 1-11.

Kirton, C.M., & Nash, G.B. ( 2000). Activated platelets adherent to an intact endothelial cell monolayer bind flowing neutrophils and enable them to transfer to the endothelial surface. Journal of Laboratory & Clinical Medicine136:303–313

Kral, J.B., et al (2016). Platelet interaction with innate immune cells.Transfus Med Hemother.;43(2):78–88. Mattoscio D, Evangelista V, De Cristofaro R, Recchiuti A, Pandolfi A, Di Silvestre S, Manarini S, Martelli N, Rocca B, Petrucci G, Angelini DF, Battistini L, Robuffo I, Pensabene T, Pieroni L, Furnari ML, Pardo F, Quattrucci S, Lancellotti S, Davì G, Romano M (2010), Cystic fibrosis transmembrane conductance regulator (CFTR) expression in human platelets: impact on mediators and mechanisms of the inflammatory response. FASEB J.; 24: 3970–3980

Mauler, M., Seyfert, J., Haenel D. Seeba, H. Guenther J., Stallmann D., Schoenichen C., Hilgendorf I., Bode, C., Ahrens I., & Duerschmied, D. (2016). Platelet-neutrophil complex formation-a detailed in vitro analysis of murine and human blood samples. Journal of Leukocyte Biology, 99(5), 781–789

Pamuk, G.E., Vural, O., Turgut, B., Demir, M., Umit, H., & Tezel, A. (2006). Increased circulating platelet-neutrophil, platelet-monocyte complexes, and platelet activation in patients with ulcerative colitis: a comparative study. Am J Hematol 81:753–759

Peters, M.J., Heyderman, R.S., Hatch, D.J., et al. (1997). Investigation of platelet-neutrophil interactions in whole blood by flow cytometry. J Immunol Methods.;209:125–135.

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Published

2021-12-15

How to Cite

Yuzeir, S., Shtereva, B., & Gercheva, L. (2021). INCREASED CIRCULATING PLATELET-NEUTROPHIL COMPLEXES IN ADULT NEWLY DIAGNOSED NON-HODGKINS‘S LYMPHOMA PATIENTS. KNOWLEDGE - International Journal , 49(4), 757–762. Retrieved from https://ikm.mk/ojs/index.php/kij/article/view/4554