Elevated Serum Exosomal miR-125b Level as a Potential Marker for Poor Prognosis in Intermediate-Risk Acute Myeloid Leukemia

Abstract

Background: The prognostic significance of miR-125b in intermediate-risk acute myeloid leukemia has not been well investigated. The aim of the study was to reveal the relationship between the elevated exosomal miR-125b level and the poor prognosis in adult patients with this disease. Methods: A total of 154 consecutive patients with intermediate-risk acute myeloid leukemia were enrolled. Exosomes were isolated from blood specimens. The exosomal miR-125b level was determined using quantitative real-time polymerase chain reaction. Patients received standardized therapy and were followed up for 1–24 months. Details about relapse and overall death were recorded. Results: Patients were divided into the high miR-125b level group (n = 77) and the low miR-125b level group (n = 77). In the multivariate Cox proportional hazard regression model, the high miR-125b level group was separately associated with increased risks of relapse and overall death in 2 years (hazard ratio [HR] 2.84, 95% CI 1.81–4.33 and HR 2.69, 95% CI 1.87–4.52). Kaplan-Meier analysis also revealed that a high miR-125b level was related to a higher cumulative relapse and overall death rates (p < 0.001 and p < 0.001, respectively). Conclusion: Circulating exosomal miR-125b concentration might be an independent prognostic indicator in intermediate-risk acute myeloid leukemia patients. An elevated miR-125b level indicated higher risks of relapse and overall death.

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

“…In particular, they found that exosomal miR-125b was higher in patients at diagnosis with respect to healthy subjects. Moreover, miR-125b increased levels correlated with higher risks of relapse and overall death, supporting its role as an independent prognostic indicator in this intermediate-risk group of patients [87].…”

“…EV miRNAs were also suggested as potential biomarkers in AML [37,81,[86][87][88]. Analysis of miR-155, a miRNA deregulated in this neoplasm [89], showed its significant higher level in serum MVs from 11 AML patients at diagnosis compared to healthy subjects; moreover, ROC curve analysis revealed that miR-155 could be a new potential diagnostic biomarker in AML [37].…”

High-throughput analysis and functional interpretation of extracellular vesicle content in hematological malignancies

“…Acute leukemia-derived EVs contain a variety of non-coding RNAs supporting leukemogenesis and influencing the outcome and response to therapy through the regulation of several genes involved in the pathogenesis of this disease [56] . In addition, several studies have highlighted the promising role of circulating miRs as biomarkers in acute myeloid leukemia (AML) ( Table 1 ) [4] , [34] , [74] , [82] , [85] . For instance, Marcucci and colleagues, by using nCounter assay, demonstrated that miR-155 overexpression was independently associated to poor prognosis in a large cohort of adult AML patients with normal karyotype [45] .…”

Exosome: From leukemia progression to a novel therapeutic approach in leukemia treatment

“…Noting that, miR-125b to be proposed as an important biomarker for predicting the rate of disease remission and the risk of relapse. 140 Attempts to use DCs for the vaccination of leukemia patients have appeared to bring some interesting results. Hus et al 141 discussed the potential effects of autologous DC-based vaccination against CLL in 2008.…”

“…Interestingly, a prior study focusing on serum exosomal miRNA‐125b in AML patients identified an up‐regulation of this miRNA to be strongly associated with elevation of relapse and risk of mortality. Noting that, miR‐125b to be proposed as an important biomarker for predicting the rate of disease remission and the risk of relapse 140 . Attempts to use DCs for the vaccination of leukemia patients have appeared to bring some interesting results.…”