PhD Scientific Days 2021

CL_V_P: Clinical Medicine V. Posters

Novel Liquid Biopsy Markers of Central Nervous System Involvement in Pediatric Acute Lymphoblastic Leukemia

Előadó neve

Dr. Balint, Egyed

Előadó munkahelye

Semmelweis University 2nd Department of Pediatrics

Előadó telefonszáma

+36206701294

Előadó e-mail címe

egyed.balint@med.semmelweis-univ.hu

Az előadás címe

Novel Liquid Biopsy Markers of Central Nervous System Involvement in Pediatric Acute Lymphoblastic Leukemia

Szerző(k) neve és munkahelye

Bálint Egyed1,2, Anna Horváth2, Nóra Kutszegi1, András Gézsi2, Judit C. Sági2, Andrea Rzepiel1, Csaba Szalai2,3, Dániel J. Erdélyi1, Ágnes F. Semsei2, Gábor Kovács1

1 2nd Department of Pediatrics, Semmelweis University, Budapest
2 Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest
3 Heim Pal National Pediatric Institute, Budapest

Bemutatás módja

Poszter

Szekció

Clinical Medicine V. Posters

Language of the presentation

English

Preferred session

Clinical Medicine

Összefoglaló szövege

Introduction: 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.

Aims: To explore more sensitive CNS status indicators, we examined microRNA (miR) expression in body fluids of patients with pediatric leukemia. The main set of proteins associated with CNS trafficking and regulated by our candidate miRs were also studied in correlation with miR expressions.

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 selected promising miR family was further scrutinized with TaqMan Advanced miRNA Assays on serial cerebrospinal fluid (CSF), bone marrow (BM) and peripheral blood samples (n=132). Next, enzyme-linked immunosorbent assays were used to measure vascular endothelial growth factor A (VEGF-A) and integrin alpha 6 (ITGA6) levels in CSF and BM samples.

Results: Regarding the discovery study, principal component analysis identified the role of miR-181-family (miR-181a, -181b, -181c) 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 patients with CNS+ ALL compared to CNS‒ cases (n=8 vs. n=10, ΔFC=52.30, p=1.5E-4). The sensitivity of CSF miR-181a measurement highly exceeded those of conventional cytospin in the initial diagnosis of CNS+ ALL (90.0% vs. 54.5%). Decrease in miR-181a level from the diagnosis of ALL to the 33rd day of therapy was also detectable in BM samples among CNS+ patients (ΔFC=-187.96, p=0.006). Analysis of CSF and BM samples of the validation cohort revealed a slight correlation between miR-181a and VEGF-A levels (n=46, Pearson’s r=0.36, p=0.015). In addition, CSF VEGF-A concentration distinguished patients with CNS+ and CNS‒ ALL (p=0.023), which is in parallel with previous preclinical data from the literature.

Conclusion: After validating in international cohorts, quantification of miR-181a and/or VEGF-A might provide novel tools to adjust CNS-directed therapy in pediatric ALL.

Funding: New National Excellence Program (ÚNKP-20-3-II-SE-20) and Co-operative Doctoral Program (KDP-2020/1008491) of the Ministry of Innovation and Technology

University and Doctoral School

Semmelweis University, Károly Rácz Doctoral School of Clinical Medicine

Supervisor

Gábor Kovács MD, DSc; Ágnes F. Semsei PhD

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6109

Start

11:46

End

11:49

Authors (legacy)

Bálint Egyed1,2, Anna Horváth2, Nóra Kutszegi1, András Gézsi2, Judit C. Sági2, Andrea Rzepiel1, Csaba Szalai2,3, Dániel J. Erdélyi1, Ágnes F. Semsei2, Gábor Kovács1

1 2nd Department of Pediatrics, Semmelweis University, Budapest
2 Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest
3 Heim Pal National Pediatric Institute, Budapest