PhD Scientific Days 2023

KDP Poster session

Beyond single genetic aberrations: an integrative copy number alteration-driven scoring guide to refine cytogenetic risk stratification in pediatric acute lymphoblastic leukemiA

Előadó neve

Dr. Egyed, Balint, PhD

Neptun code

XNQRCI

Előadó munkahelye

Department of Pediatrics

Előadó telefonszáma

+36206701294

Előadó e-mail címe

egyed.balint@semmelweis.hu

Az előadás címe

Beyond single genetic aberrations: an integrative copy number alteration-driven scoring guide to refine cytogenetic risk stratification in pediatric acute lymphoblastic leukemiA

Szerző(k) neve és munkahelye

Bálint Egyed1,2, Gábor Bedics1, Zsuzsanna Jakab3, Dániel Erdélyi2, Judit Müller2, Lili Kotmayer1, Anne Benard-Slagter4, Karel de Groot4, Szilvia Krizsán1, Anna Bekő1, Béla Kajtár5, László Pajor5, Ágnes Vojcek6, Gábor Ottóffy6, Anikó Ujfalusi7, Csongor Kiss8, Réka Simon9, Lilla Tiszlavicz10, Krisztina Csanádi11, Gergely Kriván12, Suvi Savola4, Csaba Bödör1, Gábor Kovács2, Donát Alpár1

1HCEMM-SU Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
22nd Department of Pediatrics, Semmelweis University, Budapest, Hungary
3Hungarian Childhood Cancer Registry, Hungarian Pediatric Oncology Network
4MRC Holland, Amsterdam, The Netherlands
5Department of Pathology, University of Pécs Clinical Centre, Pécs, Hungary
6Department of Pediatrics, University of Pécs Clinical Centre, Pécs, Hungary
7Department of Laboratory Medicine, University of Debrecen, Hungary
8Division of Pediatric Hematology-Oncology, Institute of Pediatrics, University of Debrecen, Debrecen, Hungary
9Hemato-Oncology and Stem Cell Transplantation Unit, Velkey László Children's Health Center, Miskolc, Hungary
10Department of Pediatrics and Pediatric Health Care Center, University of Szeged, Szeged, Hungary
11Kemény Pál Hemato-Oncology Unit, Heim Pál National Pediatric Institute, Budapest, Hungary
12Pediatric Hematology and Stem Cell Transplantation Unit, Central Hospital of Southern Pest - National Institute of Hematology and Infectious Diseases, Budapest, Hungary

Bemutatás módja

Poszter

Szekció

KDP Poster session

Language of the presentation

English

Preferred session

Clinical Medicine

Összefoglaló szövege

Introduction and aims: Recently, numerous leukemia-relevant copy number alterations (CNAs) were assessed as patient stratification tools in pediatric acute lymphoblastic leukemia (ALL). In our multicentric study of the Hungarian Pediatric Leukemia Molecular Profiling Program, we aimed to integrate classical cytogenetic risk factors with CNA profiles for survival prediction.
Methods: Diagnostic bone marrow samples from 260 children with precursor B-cell ALL were comprehensively screened by digital multiplex ligation-dependent probe amplification (digitalMLPA, MRC Holland) using ALL-specific D007 probemixes on Illumina MiSeq platform. Bioinformatic analysis was performed using the Coffalyser software (MRC Holland).
Results: On average, 5.4 CNAs (gross chromosomal and subchromosomal aberrations) were detected per patient with a mean of 2.5 subchromosomal alterations. Among patients with high hyperdiploid (HHD) karyotype, the concurrent gain of chromosome 4 and 6 proved to be a highly favorable predictor (5-year EFS: 93.2%, other HHD patients: 60.4%; p=0.0005). Several subchromosomal CNAs in disease-relevant genes were identified (e.g. CDKN2A/B in 45.6% of patients, PAX5 13.4%, IKZF1 11.5%). Prognostic categories defined by CNAs in IKZF1 and related genes (normal or deleted IKZF1, IKZF1plus) were refined considering the cytogenetic risk groups suggested by Moorman et al., which resulted in a more accurate risk stratification (IKAROS-low vs. IKAROS-intermediate, p=0.002; IKAROS-intermediate vs. IKAROS-high, p=0.048). Finally, we created a novel integrated score system by proportionally weighting individual cytogenetic aberrations and subchromosomal CNAs (e.g. harboring ETV6-RUNX1 counts +1.5 points; TP53 deletion: -0.25 points). Patient-specific cumulative scores generated from the prognostic value of single lesions distinguished two favorable (60% of patients; excellent and low risk, 96.1% and 87.9% 5-year EFS; p=0.041) and two unfavorable (40% of patients; high and ultra-poor risk, 64.3% and 30.6% 5-year EFS; p=0.004) prognostic groups.
Conclusions: DigitalMLPA offers a fast and standardizable DNA copy number analysis, which is implementable in the diagnostic workflow of pediatric ALL and expands genetics-based risk prediction perspectives.
Funding: ÚNKP-22-4-I-SE-11, FK20-134253, K21-137948, H2020-739593, KDP-2020-1008491

University and Doctoral School

Semmelweis University, Károly Rácz Doctoral School of Clinical Medicine

Supervisor

Prof. Dr. Gábor Kovács

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

6109

Start

09:18

End

09:23

Authors (legacy)

Bálint Egyed1,2, Gábor Bedics1, Zsuzsanna Jakab3, Dániel Erdélyi2, Judit Müller2, Lili Kotmayer1, Anne Benard-Slagter4, Karel de Groot4, Szilvia Krizsán1, Anna Bekő1, Béla Kajtár5, László Pajor5, Ágnes Vojcek6, Gábor Ottóffy6, Anikó Ujfalusi7, Csongor Kiss8, Réka Simon9, Lilla Tiszlavicz10, Krisztina Csanádi11, Gergely Kriván12, Suvi Savola4, Csaba Bödör1, Gábor Kovács2, Donát Alpár1

1HCEMM-SU Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
22nd Department of Pediatrics, Semmelweis University, Budapest, Hungary
3Hungarian Childhood Cancer Registry, Hungarian Pediatric Oncology Network
4MRC Holland, Amsterdam, The Netherlands
5Department of Pathology, University of Pécs Clinical Centre, Pécs, Hungary
6Department of Pediatrics, University of Pécs Clinical Centre, Pécs, Hungary
7Department of Laboratory Medicine, University of Debrecen, Hungary
8Division of Pediatric Hematology-Oncology, Institute of Pediatrics, University of Debrecen, Debrecen, Hungary
9Hemato-Oncology and Stem Cell Transplantation Unit, Velkey László Children's Health Center, Miskolc, Hungary
10Department of Pediatrics and Pediatric Health Care Center, University of Szeged, Szeged, Hungary
11Kemény Pál Hemato-Oncology Unit, Heim Pál National Pediatric Institute, Budapest, Hungary
12Pediatric Hematology and Stem Cell Transplantation Unit, Central Hospital of Southern Pest - National Institute of Hematology and Infectious Diseases, Budapest, Hungary