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

Abstract

In the era of precision medicine, liquid biopsy is becoming increasingly important in oncology. It consists in the isolation and analysis of tumor-derived biomarkers, including extracellular vesicles (EVs), in body fluids. EVs are lipid bilayer-enclosed particles, heterogeneous in size and molecular composition, released from both normal and neoplastic cells. In tumor context, EVs are valuable carriers of cancer information; in fact, their amount, phenotype and molecular cargo, including proteins, lipids, metabolites and nucleic acids, mirror nature and origin of parental cells rendering EVs appealing candidates as novel biomarkers. Translation of these new potential diagnostic tools into clinical practice could deeply revolutionize the cancer field mainly for solid tumors but for hematological neoplasms, too.

Fig. 1. Role of EV repertoire and potential clinical applications in cancer.

EV cargo includes bioactive molecules on EV surface (adhesion molecules, tetraspanins, molecules involved in antigen presentation, proteoglycans, lipids, P-glycoprotein P-gp and tumor specific antigens) and molecular content (DNA, mRNA, microRNA, long noncoding RNA, short noncoding RNA, circular RNA, metabolites, heat shock proteins, enzymes). EVs and their components play multiple roles in cancer and have peculiar physicochemical characteristics, thus holding a potential clinical utility as biomarkers as well as therapeutic targets and agents.

Fig. 2. Advantages and disadvantages of current and near future diagnostic tools in hematological malignancies.

Diagnostics of hematological malignancies is currently based on bone marrow (BM) and peripheral blood (PB) analyses. BM biopsy presents several disadvantages (in red), such as localized sampling bias, invasiveness, risk and pain, and spatial limitation. PB analysis overcomes BM limitations, being tumor representative, noninvasive, easily and fast to obtain. Sampling of both BM and PB sources allow the analysis of tumor cells that are not always abundant. Liquid biopsy represents a near future diagnostic tool and includes analysis of circulating tumor cells, nucleic acids and/or EVs. These last analytes are the most abundant and stable in PB and are characterized by an enriched molecular cargo which can be considered representative of the cells of origin.