MiR-128-3p as blood based liquid biopsy biomarker in childhood acute lymphoblastic leukemia

Andrea Rzepiel; Anna Horváth; Nóra Kutszegi; András Gézsi; Judit C Sági; Laura Almási; Bálint Egyed; Péter Lőrincz; Tamás Visnovitz; Gábor T Kovács; Csaba Szalai; Ágnes F Semsei; Dániel J Erdélyi

doi:10.1016/j.mcp.2023.101893

MiR-128-3p as blood based liquid biopsy biomarker in childhood acute lymphoblastic leukemia

Mol Cell Probes. 2023 Feb:67:101893. doi: 10.1016/j.mcp.2023.101893. Epub 2023 Jan 11.

Authors

Affiliations

¹ Dept. of Paediatrics, Semmelweis University, Budapest, Hungary.
² Dept. of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary; HCEMM-SE Molecular Oncohematology Research Group, 1st Dept. of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
³ Dept. of Paediatrics, Semmelweis University, Budapest, Hungary; Dept. of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
⁴ Dept. of Measurement and Information Systems, Budapest University of Technology and Economics, Budapest, Hungary.
⁵ Dept. of Paediatrics, Semmelweis University, Budapest, Hungary; Dept. of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary; Institute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, Hungary.
⁶ Dept. of Paediatrics, Semmelweis University, Budapest, Hungary; Dept. of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary; HCEMM-SE Molecular Oncohematology Research Group, 1st Dept. of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
⁷ Dept. of Anatomy, Cell and Developmental Biology, ELTE Eötvös Loránd University, Budapest, Hungary.
⁸ Dept. of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary; Dept. of Plant Physiology and Molecular Plant Biology, ELTE Eötvös Loránd University, Budapest, Hungary.
⁹ Dept. of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary; Heim Pál Children Hospital, Budapest, Hungary.
¹⁰ Dept. of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary. Electronic address: semsei.agnes@med.semmelweis-univ.hu.

PMID: 36640912
DOI: 10.1016/j.mcp.2023.101893

Abstract

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 (r_EEF = 0.99, p_EEF = 1.13E-9 and r_PFP = 0.99, p_PFP = 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 (r_EEF = 0.96; p_EEF = 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.

Keywords: Childhood acute lymphoblastic leukemia; Exosome-enriched fraction; microRNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor
Child
Humans
MicroRNAs* / metabolism
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / diagnosis
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / pathology
Precursor Cell Lymphoblastic Leukemia-Lymphoma* / diagnosis
Precursor Cell Lymphoblastic Leukemia-Lymphoma* / pathology

Substances

Biomarkers, Tumor
MicroRNAs
MIRN128 microRNA, human