High serum levels of extracellular vesicles expressing malignancy-related markers are released in patients with various types of hematological neoplastic disorders

Abstract

Many cell types release extracellular vesicles (EVs), including exosomes, microvesicles (MVs), and apoptotic bodies, which play a role in physiology and diseases. Presence and phenotype of circulating EVs in hematological malignancies (HMs) remain largely unexplored.The aim of this study was to characterize EVs in peripheral blood of HM patients compared to healthy subjects (controls). We isolated serum EVs from patients with chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL), Waldenstrom's macroglobulinemia (WM), Hodgkin's lymphoma (HL), multiple myeloma (MM), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDS), and controls. EVs were isolated from serum of peripheral blood by ultracentrifuge steps and analyzed by flow cytometry to define count, size, and immunophenotype. MV levels were significantly elevated in WM, HL, MM, AML, and some MPNs and, though at a lesser degree, in CLL and NHL as compared to healthy controls. HL, MM, and MPNs generated a population of MVs characterized by lower size (below 0.3 μm) when compared to controls. MVs from patients specifically expressed tumor-related antigens, such as CD19 in B cell neoplasms, CD38 in MM, CD13 in myeloid tumors, and CD30 in HL. Both total and antigen-specific count of MVs significantly correlated with different HM clinical features such as Rai stage in CLL, International Prognostic Scoring System in WM, International Staging System in MM, and clinical stage in HL. MVs may represent a novel biomarker in HMs.

More Than Tiny Sacks

“…In constrastsystemic administration via intravenous 131 infusion affords the provision for repeated exosome dosage but may carry the risk of ‘off target effects’ in other organs besides the heart. Similarly, it has been shown that intracoronary transfer of stem cells results in migration of the cells across the vessel barrier and into the neighboring myocardium 132, 133 providing the rationale for a similar delivery method for exosomes in the future. Optimal exosome based treatment would warrant ‘ tailored exosomes’ designed for specific cell types within an organ to minimize adverse effects but this approach has not been tested yet and certainly represents a limitation.…”

“…Indeed, it is reported that routine examination of serum from patients with different malignant disorders reveals high expression of extracellular vesicles that display malignancy-related disorders 133 . Similarly, cardiac hypertrophy has been associated with release of exosome from the heart that carry functional angiotensin II type I receptor (AT1R) 137 .…”

Non-Proximal Renal Tubule-Derived Urinary Exosomal miR-200b as a Biomarker of Renal Fibrosis

“…The results showed that the number of extracellular vesicles was substantially higher in the prostate cancer patient group than in the healthy control group. Caivano et al [22] used flow cytometry to count the number of microvesicles and showed that the number was higher in subjects with hematological malignancies than in healthy individuals. The number of exosomes/microvesicles is useful not only as a diagnostic marker of tumors but also as a marker of progression and prognosis.…”

Extracelluláris vesiculák és hematológiai malignitásokban játszott szerepük

“…Jóval kevesebb vizsgálat folyt hematológiai malignitások és az extracelluláris vesiculák kapcsolatára vonatkozóan [20,[26][27][28][29]. Ezeket mutatjuk be összefoglalónk hátralévő részében.…”

“…Diagnóziskor és a kezelés egyes szakaszai során, majd a kezelés végén AML-es betegek véréből nyert exosomák fehérjemintázata jellegzetes különbségeket mutatott. E közlemények felvetik, hogy az extracelluláris vesiculákat biomarkerként hasznosíthatnánk hematológiai malignitások diagnosztikájában, a maradék betegség kö-vetésére [18,26,29,37]. A vér vagy a vizelet vesiculáinak vizsgálata lényegesen kevésbé invazív mintavételt igényel-ne, mint sok más, jelenleg rutin-vizsgálóeljárás.…”