High Level of Circulating Microparticles in Patients with BCR/ ABL Negative Myeloproliferative Neoplasm – a Pilot Study

Abstract

Background: Microparticles (MPs) are small (0.1-1 μm) cell-derived vesicles released during activation or apoptosis, with a surface-exposed phosphatidylserine along with antigens indicat ing the cellular origin. The level of MPs is known to be elevated in thromboembolic dis eases and malignancies; it is believed that MPs are not only amplify ing but can also initiate the thrombogenesis processes. BCR/ ABL negative myeloproliferative neoplasms (MPNs) are clonal haematopoietic dis eases, which include polycythemia vera, essential thrombocythemia and primary myelofibrosis. One of the main problems of MPN patients is high risk and incidence of thrombosis which affect the survival, quality of life and life expectancy. Patients and methods: The clinical significance of circulat ing MPs was assessed in a group of 179 patients with BCR/ ABL-negative MPNs. Analysis of MPs was done us ing flow cytometry on 417 samples, and MPs procoagulation activity was performed us ing a functional assay called Zymuphen MP-activity (Hyphen Biomed, Neuville-sur-oise, France) on 274 samples. Results: Significantly higher absolute and relative count of platelet MPs was found in MPN patients when compared with healthy group, respectively (p = 0.001, p = 0.043). Erythrocyte MPs were also significantly higher in MPN patients than in the healthy group (p < 0.001). Procoagulation activity of MPs was as well significantly higher in patients compared to the control group (p < 0.001). Patients with primary myelofibrosis had decreased absolute and relative count of platelet MPs compared to polycythemia vera and essential thrombocythemia patients, respectively (p = 0.008, p = 0.014). Presence of JAK2V617F mutation was associated with higher absolute and relative count of platelet MPs, respectively (p = 0.045, p = 0.029). Conclusion: Although some literature data support the hypothesis of a direct relation between MPs and thrombotic events in MPN patients, further studies are needed to evaluate the clinical implication of MPs in the hypercoagulation state of MPN patients.

Liquid Biopsy and Potential Liquid Biopsy-Based Biomarkers in Philadelphia-Negative Classical Myeloproliferative Neoplasms: A Systematic Review

“…After we excluded the irrelevant manuscripts based on the screening of their titles and abstracts ( n = 81), we examined the full texts of 33 manuscripts. Finally, after we applied the exclusion and inclusion criteria, 27 original articles were included in this review [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ].…”

“…The analyzed studies investigated the levels of cell-free DNA ( n = 1), extracellular vesicles ( n = 7), microparticles ( n = 14) or circulating endothelial cells ( n = 5) levels in MPNs. Flow cytometry was by far the most employed method of detection ( n = 23) [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ].…”

“…A total of 14 studies focused on the role of MPs originated from platelets (PMPs), red blood cells (RMPs), granulocytes (GMPs), monocytes (MMPs), the endothelium (EMPs) or on MPs expressing the tissue factor (TF+MPs), platelet microaggregates (PMAs), platelet-monocyte conjugates (PMCs), platelet-neutrophil conjugates (PNCs) or activated platelets (APs) [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ].…”

Clinical relevance of extracellular vesicles in hematological neoplasms: from liquid biopsy to cell biopsy

“…Among myeloproliferative neoplasms (MPNs), due to their overlapping features, polycythemia vera, essential thrombocythemia (ET), and primary myelofibrosis have been traditionally grouped into a unique category of Ph − classical MPNs [94]. One of the main problems of MPN patients is the high risk and incidence of thrombosis which affects survival, quality of life, and life expectancy [96].…”

“…In particular, MPs derived from different cell sources, such as platelet-, erythrocyte-, red blood cell-, and endothelial-MPs, were found significantly augmented in MPN patients compared with healthy subjects. Interestingly, blood MP levels are positively correlated with the occurrence of thrombotic complications in MPN patients [96][97][98]. In addition, another recent study analyzed plasma levels of tissue factor positive-MPs from 59 MPN patients at diagnosis and during clinical course of disease, and showed that their procoagulant activity was significantly higher in patients suffering thrombotic events than in patients without such events.…”