MicroRNA-181a as novel liquid biopsy marker of central nervous system involvement in pediatric acute lymphoblastic leukemia.
J Transl Med
; 18(1): 250, 2020 06 22.
Article
de En
| MEDLINE
| ID: mdl-32571344
ABSTRACT
BACKGROUND:
Refractory central nervous system (CNS) involvement is among the major causes of therapy failure in childhood acute leukemia. Applying contemporary diagnostic methods, CNS disease is often underdiagnosed. To explore more sensitive and less invasive CNS status indicators, we examined microRNA (miR) expressions and extracellular vesicle (EV) characteristics.METHODS:
In an acute lymphoblastic leukemia (ALL) discovery cohort, 47 miRs were screened using Custom TaqMan Advanced Low-Density Array gene expression cards. As a validation step, a candidate miR family was further scrutinized with TaqMan Advanced miRNA Assays on serial cerebrospinal fluid (CSF), bone marrow (BM) and peripheral blood samples with different acute leukemia subtypes. Furthermore, small EV-rich fractions were isolated from CSF and the samples were processed for immunoelectron microscopy with anti-CD63 and anti-CD81 antibodies, simultaneously.RESULTS:
Regarding the discovery study, principal component analysis identified the role of miR-181-family (miR-181a-5p, miR-181b-5p, miR-181c-5p) in clustering CNS-positive (CNS+) and CNS-negative (CNSâ) CSF samples. We were able to validate miR-181a expression differences it was about 52 times higher in CSF samples of CNS+ ALL patients compared to CNSâ cases (n = 8 vs. n = 10, ΔFC = 52.30, p = 1.5E-4), and CNS+ precursor B cell subgroup also had ninefold higher miR-181a levels in their BM (p = 0.04). The sensitivity of CSF miR-181a measurement in ALL highly exceeded those of conventional cytospin in the initial diagnosis of CNS leukemia (90% vs. 54.5%). Pellet resulting from ultracentrifugation of CNS+ CSF samples of ALL patients showed atypical CD63-/CD81- small EVs in high density by immunoelectron microscopy.CONCLUSIONS:
After validating in extensive cohorts, quantification of miR-181a or a specific EV subtype might provide novel tools to monitor CNS disease course and further adjust CNS-directed therapy in pediatric ALL.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
MicroARN
/
Leucémie-lymphome lymphoblastique à précurseurs B et T
Type d'étude:
Prognostic_studies
Limites:
Child
/
Humans
Langue:
En
Journal:
J Transl Med
Année:
2020
Type de document:
Article
Pays d'affiliation:
Hongrie