PhD Scientific Days 2023

Molecular Sciences - Posters K

Identification of a potential novel biomarker for the assessment of central nervous system involvement in pediatric acute lymphoblastic leukemia

Előadó neve

Dr. Borbála, Péterffy

Neptun code

CR1YKK

Előadó munkahelye

Semmelweis University, Department of Pathology and Experimental Cancer Research

Előadó telefonszáma

+36304309791

Előadó e-mail címe

peterffy.borbala@stud.semmelweis.hu

Az előadás címe

Identification of a potential novel biomarker for the assessment of central nervous system involvement in pediatric acute lymphoblastic leukemia

Szerző(k) neve és munkahelye

Borbála Péterffy1, Tamás Nádasi2, Réka Jójárt2, Judit Müller2, Szilvia Krizsán1,2, György Péter3, Krisztina Csanádi3, Gergely Kriván4,5, Gábor Kovács2, András Matolcsy1, Dániel Erdélyi2, Csaba Bödör1, Bálint Egyed1,2,5 *, Donát Alpár1 *

1HCEMM-SU Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary; 2Second Department of Pediatrics, Semmelweis University, Budapest, Hungary; 3Hemato-Oncology Unit, Heim Pal Children's Hospital, Budapest, Hungary; 4Pediatric Hematology and Stem Cell Transplantation Department, Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary; 5Hungarian Pediatric Oncology Network
*The authors equally contributed to this work.

Bemutatás módja

Poszter

Szekció

Molecular Sciences - Posters K

Language of the presentation

English

Preferred session

Molecular Sciences

Összefoglaló szövege

Despite remarkable improvements in survival rates of patients with pediatric acute lymphoblastic leukemia (ALL), central nervous system (CNS) involvement is still associated with inferior outcome. Currently used cell-based methods can detect circulating blasts in the cerebrospinal fluid (CSF) but malignant cells attached to the meninges may remain undetected.
We aimed to identify a biomarker in the cell-free fraction of the cerebrospinal fluid that could serve as an indicator of CNS involvement in pediatric ALL.
MicroRNAs were isolated from CSF samples of children with ALL obtained at the time of diagnosis (n=19) or subsequently in the course of treatment (n=48). Copy numbers of miR-181a, miR-532 and miR-16 were quantified using digital droplet PCR (QX200 System, Bio-Rad). The association between normalized miRNA copy numbers, the level of CNS involvement and mutational status assessed by profiling diagnostic bone marrow samples was evaluated using hierarchical clustering, multiple regression and ANOVA.
Based on distinct CNS involvement revealed by cellular diagnostics, we classified patients into CNS- and CNS+ groups. Additional grouping approaches alternative to the current clinical standard were also tested utilizing hierarchical clustering on diagnostic samples of 19 individuals. Based on miR-181a expression, the majority of CNS+ patients (all but one) clustered together with 4 additional patients, who lacked any clinical evidence of CNS involvement. Considering this result, we established 3 groups: CNS-L (CNS-, low miR-181a expression), CNS-I (CNS-, intermediate miR-181a expression, clustered with CNS+ patients), and CNS-H (CNS+, high miR-181a expression). Expression of miR-181a in the CNS-I and CNS-H groups was significantly different from CNS-L patients after analyzing all samples (n=67, CNS-I vs. CNS-L p=0.020; CNS-H vs. CNS-L p=0.041), or diagnostic samples only (n=19, CNS-I vs. CNS-L p=0.010; CNS-H vs. CNS-L p=0.027). Mutations affecting the SH2B3 gene were exclusively observed in patients classified in the CNS-I and CNS-H groups.
The expression of miR-181a may serve as a reliable diagnostic marker for leukemic infiltration. Further quest for the role of SH2B3 gene in CNS invasion may be warranted.
Funding: FK20_134253 K21_137948 H2020-739593 BO/00125/22 ÚNKP-22-5-SE-7 EFOP-3.6.3-VEKOP-16-2017-00009 STIA-KFI-2022, Richter Talent Scholarship, Hungarian Pediatric Oncology Network

University and Doctoral School

Semmelweis University, Doctoral School of Pathological Sciences

Supervisor

Donát Alpár

Publication of my abstract

I do not 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

6924

Start

11:36

End

11:41

Authors (legacy)

Borbála Péterffy1, Tamás Nádasi2, Réka Jójárt2, Judit Müller2, Szilvia Krizsán1,2, György Péter3, Krisztina Csanádi3, Gergely Kriván4,5, Gábor Kovács2, András Matolcsy1, Dániel Erdélyi2, Csaba Bödör1, Bálint Egyed1,2,5 *, Donát Alpár1 *

1HCEMM-SU Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary; 2Second Department of Pediatrics, Semmelweis University, Budapest, Hungary; 3Hemato-Oncology Unit, Heim Pal Children's Hospital, Budapest, Hungary; 4Pediatric Hematology and Stem Cell Transplantation Department, Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary; 5Hungarian Pediatric Oncology Network
*The authors equally contributed to this work.