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

Abstract

Myeloproliferative neoplasms (MPNs) are rare, clonal disorders of the hematopoietic stem cell in which an uncontrolled proliferation of terminally differentiated myeloid cells is noted. Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are included in the category of Philadelphia-negative, so-called classical MPNs. The potential applications of liquid biopsy and liquid biopsy-based biomarkers have not been explored in MPNs until now. Thus, a systematic search was computed in PubMed/MEDLINE, Web of Science and The Cochrane Library and, in total, 198 potentially relevant papers were detected. Following the removal of duplicates (n = 85), 113 records were screened. After the exclusion of 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. Overall, the data analyzed in this review point out that liquid biopsy and liquid biopsy-based biomarkers (cell-free DNA, extracellular vesicles, microparticles, circulating endothelial cells) could be used in MPNs for diagnostic and prognostic purposes. Future research is needed to clarify whether this technique can be employed to differentiate between MPN subtypes and secondary causes of erythrocytosis, thrombocytosis and myelofibrosis, as well as to predict the development of thrombosis.

Coexistence of Primary Myelofibrosis and Paroxysmal Nocturnal Hemoglobinuria Clone with JAK2 V617F, U2AF1 and SETBP1 Mutations: A Case Report and Brief Review of Literature

“…In MPN patients with a high risk of thrombosis, useful prognostic and predictable biomarkers are needed. Recently, there have been reports suggesting the potential for diagnosing MPN and predicting thrombosis as a biomarker using liquid biopsy and liquid biopsy-based biomarkers in MPNs [ 33 ]. In MPN patients experiencing thrombosis, cell-free DNA, circulating endothelial cells, microparticles (MPs), tissue factors with MPs and procoagulant activity of MPs in peripheral blood were increased and platelet-derived MPs was decreased [ 33 ].…”

“…Recently, there have been reports suggesting the potential for diagnosing MPN and predicting thrombosis as a biomarker using liquid biopsy and liquid biopsy-based biomarkers in MPNs [ 33 ]. In MPN patients experiencing thrombosis, cell-free DNA, circulating endothelial cells, microparticles (MPs), tissue factors with MPs and procoagulant activity of MPs in peripheral blood were increased and platelet-derived MPs was decreased [ 33 ]. When there are complex prognostic factors, such as in this case, biomarkers derived from liquid biopsy have the potential to help predict the prognosis.…”

Megakaryopoiesis and Platelet Biology: Roles of Transcription Factors and Emerging Clinical Implications

“…Importantly, platelet-derived MV/MPs showed procoagulant and prothrombotic activities, which indicate that the risk of thrombosis in ET is correlated with the amount of platelet-derived MV/MPs [161]. Thus, it has been suggested that measurement of the MV/MPs for diagnosis of MPN, ET, or the thrombosis risk of ET might be feasible via liquid biopsy [162].…”

Urinary Extracellular Vesicles Are a Novel Tool to Monitor Allograft Function in Kidney Transplantation: A Systematic Review

“…However, a for-cause biopsy is costly and invasive, and this has fueled a continuing search for alternative biomarkers. Currently, non-invasive liquid biopsy and liquid biopsy-based biomarkers, e.g., cell-free DNA and extracellular vesicles (EVs), have shown an extremely high diagnostic value in various disorders, including malignancies, autoimmune diseases, organ dysfunction, and transplantation [ 6 , 7 ]. In this manuscript, we discuss how measurements of EVs could provide additional information about kidney function, thereby avoiding the need for an invasive biopsy [ 8 ].…”