Characterization and prognostic relevance of circulating microvesicles in chronic lymphocytic leukemia

Abstract

Microvescicles (MV) are shedding particles released by normal and neoplastic cells, whose levels in biological fluids highlight their potential role as disease biomarkers and therapeutic targets. By analyzing 131 newly diagnosed chronic lymphocytic leukemia (CLL), we found that the absolute number of serum CLL MV was significantly higher than in controls, in particular in advanced stages of disease. In addition, CD19 + and CD37+, B-cell derived MV, significantly correlated with high tumor burden. Absolute MV number cutoff selected by ROC analysis distinguished Rai stage 0 patients with shorter time to treatment (TTT) from those with more stable disease. Likewise, in the entire cohort, two groups of patients with different overall survival (OS) and different TTT were identified. At multivariate analysis, serum MV independently predicted for OS (along with Rai stage) and TTT (along with Rai stage, lymphocytes and CD38). In conclusion, circulating MV represent a new potential prognostic biomarker in CLL.

Microvesicles released from multiple myeloma cells are equipped with ectoenzymes belonging to canonical and non-canonical adenosinergic pathways and produce adenosine from ATP and NAD+

“…Among other surface molecules, MVs express integrins, selectins, CD40 or CD81, and are involved in inter-cellular communications, being captured by target cells through endocytosis, receptor-mediated endocytosis or fusion with the plasma membrane. 18,19 Tumor-derived EV are reported as involved in disease progression [20][21][22] and as dampening anti-tumor immune response. 17,18 Involvement of MVs in tissue damage 23 and disease progression.…”

Microvesicles expressing adenosinergic ectoenzymes and their potential role in modulating bone marrow infiltration by neuroblastoma cells

“…They may be captured by distinct target cells through spontaneous or receptormediated endocytosis, or by direct fusion with the plasma membrane. 28 EV released by tumor cells are reported to be involved in disease progression, [29][30][31] through the inhibition of anti-tumor immune response. 25,27 Recent studies on exosomes obtained from NB demonstrated that they can transfer oncogenic microRNAs to normal cells, contributing to metastasis and resistance to chemotherapy.…”

Extracellular Vesicles After Allogeneic Hematopoietic Cell Transplantation: Emerging Role in Post-Transplant Complications

“…Extracellular vesicles could also be used as biomarkers to monitor disease persistence or promptly detect early signs of relapse before and after HCT. In this context, higher levels of EVs in patients' sera compared to healthy donors are detected in many hematological malignancies (115)(116)(117)(118). Moreover, changes in absolute EV counts and EV protein contents have been observed after induction chemotherapy and corresponded to blast reduction in the BM (117,119).…”