Details

Autor(en) / Beteiligte

• Egyed, Bálint
• Kutszegi, Nóra
• Sági, Judit C
• Gézsi, András
• Rzepiel, Andrea
• Visnovitz, Tamás
• Lőrincz, Péter
• Müller, Judit
• Zombori, Marianna
• Szalai, Csaba
• Erdélyi, Dániel J
• Kovács, Gábor T
• Semsei, Ágnes F

Titel

MicroRNA-181a as novel liquid biopsy marker of central nervous system involvement in pediatric acute lymphoblastic leukemia

Ist Teil von

• Journal of translational medicine, 2020-06, Vol.18 (1), p.250-250, Article 250

Ort / Verlag

England: BioMed Central Ltd

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek

Beschreibungen/Notizen

• 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. 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. 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 (CNS ) 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 CNS 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. 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.