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MiR-128-3p as blood based liquid biopsy biomarker in childhood acute lymphoblastic leukemia
Andrea Rzepiel1, Anna Horváth2, Nóra Kutszegi3
1Dept. of Paediatrics, Semmelweis University, Budapest, Hungary.
Background:
Minimal residual disease (MRD) is one of the most valuable independent prognostic factors in acute lymphoblastic leukemia (ALL). Bone marrow (BM) aspiration, however, is an invasive process. Previous studies have shown that microRNAs (miR) and extracellular vesicle (EV)-related miRs show different expression profiles at the presence of malignant cells compared to healthy controls. In our previous project, we have reported that two miRs previously described to be overexpressed in blasts were significantly decreased over the first week of the therapy of patients with ALL in the platelet free plasma fraction (PFP) of peripheral blood samples (PB). The aim of the current study was to assess the relation between day 15 flow cytometry (FC) MRD and expression of miR-128-3p and miR-222-3p miRs in exosome-enriched fraction (EEF) of PFP to evaluate whether their expression in EEF correlates with day 15 FC MRD more precisely.
Methods:
PB was collected from 13 patients diagnosed with pediatric pre-B ALL at 4 time points. Expression of miR-128-3p and miR-222-3p was measured by qPCR in PFP and EEF.
Results:
Positive correlation was found between changes of miR-128-3p expression in EEF or PFP by day 8 of chemotherapy and day 15 FC MRD (rEEF = 0.99, pEEF = 1.13E-9 and rPFP = 0.99, pPFP = 4.75E-9, respectively). Furthermore, the decrease of miR-128-3p in EEF by day 15 of treatment also showed a positive correlation with day 15 FC MRD (rEEF = 0.96; pEEF = 4.89E-5).
Conclusion:
Our results show that circulating miRs are potential biomarkers of ALL MRD, asmiR-128-3p level both in PFP and EEF predicts day 15 FC MRD. In addition, the assessment of the EEF gave a more promising result.
Insights
Minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) can be monitored non-invasively. Circulating microRNAs (miRs), specifically miR-128-3p in platelet-free plasma (PFP) and exosome-enriched fractions (EEF), show strong correlation with MRD levels.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Minimal residual disease (MRD) is a key prognostic factor in acute lymphoblastic leukemia (ALL).
- Bone marrow aspiration for MRD assessment is invasive.
- Extracellular vesicle-related microRNAs (miRs) show altered expression in malignant conditions.
Purpose of the Study:
- To evaluate the correlation between miR-128-3p and miR-222-3p expression in peripheral blood fractions and day 15 flow cytometry (FC) MRD in pediatric ALL patients.
- To determine if exosome-enriched fraction (EEF) of platelet-free plasma (PFP) provides a more precise assessment of MRD compared to PFP alone.
Main Methods:
- Peripheral blood (PB) samples were collected from 13 pediatric pre-B ALL patients at 4 time points.
- Quantitative PCR (qPCR) was used to measure miR-128-3p and miR-222-3p expression in PFP and EEF.
- Correlation analysis was performed between miR expression levels and day 15 FC MRD.
Main Results:
- A strong positive correlation was observed between changes in miR-128-3p expression in EEF and PFP by day 8 of chemotherapy and day 15 FC MRD (r=0.99).
- A decrease in miR-128-3p in EEF by day 15 also strongly correlated with day 15 FC MRD (r=0.96).
Conclusions:
- Circulating miR-128-3p in both PFP and EEF are potential biomarkers for predicting ALL MRD.
- The assessment of miR-128-3p in the exosome-enriched fraction (EEF) of PFP shows promising results for MRD monitoring in ALL.
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