PhD Scientific Days 2024

Poster Session Q - Pathological and Oncological Sciences 2.

Identifing novel biomarkers in pediatric acute lymphoblastic leukemia through comprehensive genomic and transcriptomic profiling

Előadó neve

Dr. Péterffy, Borbála

Neptun code

CR1YKK

Előadó munkahelye

Semmelweis University, Department of Pathology and Experimental Cancer Research

Előadó telefonszáma

06304309791

Előadó e-mail címe

peterffy.borbala@stud.semmelweis.hu

Az előadás címe

Identifing novel biomarkers in pediatric acute lymphoblastic leukemia through comprehensive genomic and transcriptomic profiling

Szerző(k) neve és munkahelye

Borbála Péterffy¹, Szilvia Krizsán², Gábor Bedics¹, Anna Bekő¹, Bálint Egyed³, Lajos László Hegyi¹, Dániel János Erdélyi³, Judit Müller³, Zsuzsanna Jakab³, Tibor Nagy⁴, György Péter⁵, Krisztina Csanádi⁵, Gábor Ottóffy⁶, Katalin Csernus⁶, Ágnes Vojcek⁶, Lilla Györgyi Tiszlavicz⁷, Krisztina Mita Gábor⁷, Ágnes Kelemen⁸, Péter Hauser⁸, Krisztián Kállay⁹, Gabriella Kertész⁹, Zsuzsanna Gaál¹⁰, István Szegedi¹⁰, Gábor Barna¹, Ágnes Márk¹, Zsuzsanna Hevessy¹¹, Anikó Ujfalusi¹¹, Béla Kajtár¹², Csongor Kiss¹⁰, Gergely Kriván⁹, András Matolcsy¹³, Gábor Kovács³, Csaba Bödör¹³, Donát Alpár¹³

1: Department of Pathology and Experimental Cancer Research, Semmelweis University
2: Department of Pathology and Experimental Cancer Research, Department of Pediatrics, Semmelweis University
3: Department of Pediatrics, Semmelweis University
4: Department of Biochemistry and Molecular Biology, University of Debrecen
5: Hemato-Oncology Unit, Heim Pál Children's Hospital
6: Department of Pediatrics, Oncohaematology Division, University of Pécs Medical School
7: Department of Pediatrics and Pediatric Health Care Center, Faculty of Medicine, University of Szeged
8: Velkey László Child's Health Center, Borsod-Abaúj-Zemplén County Central Hospital and University Teaching Hospital
9: Pediatric Hematology and Stem Cell Transplantation Department, Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases
10: Department of Pediatric Hematology-Oncology, Institute of Pediatrics, Faculty of Medicine, University of Debrecen
11: Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen
12: Department of Pathology, University of Pécs Medical School
13: Pathology and Experimental Cancer Research, Semmelweis University

Bemutatás módja

Poszter

Szekció

Poster Session Q - Pathological and Oncological Sciences 2.

Language of the presentation

English

Preferred session

Pathological and Oncological Sciences

Összefoglaló szövege

Introduction: Recent progress in therapeutic approaches for pediatric acute lymphoblastic leukemia (ALL) improved 5-year survival rates significantly; however, certain genetically defined subgroups still exhibit considerably shorter survival.
Aims: Our objective was to investigate the genomic and transcriptomic landscape of Hungarian children diagnosed with ALL in order to uncover alterations with prognostic and therapeutic implications.
Methods: Diagnostic bone marrow samples were investigated from 180 patients diagnosed with B-ALL (n=150) or T-ALL (n=30). Gene fusions were identified with targeted RNA-sequencing (Illumina, TruSight RNA Pan-cancer Panel), while mutation screening was performed using a custom QIASeq Targeted DNA Panel covering 102 disease-relevant genes. Copy number alterations were screened with multiplex ligation-dependent probe amplification (MLPA).
Results: Gene fusions were detected in 34.9% of patients with B-ALL and 46.4% of patients with T-ALL. The most prevalent gene fusions observed were ETV6::RUNX1, STIL::TAL1, P2RY8::CRLF2, and TCF3::PBX1. Additionally, five novel fusions, involving JAK2, PAX5, KMT2A, and RUNX1 genes were detected. In B-ALL, variants most frequently affected RAS-pathway genes (KRAS, NRAS, FLT3), while NOTCH1, PHF6, PTEN and WT1 were the most commonly altered genes in T-ALL. IKZF1 deletion was observed in 15.8% of B-ALL patients, with seven of them showing IKZF1plus genotype. Mutations in the UBA2 gene occurred predominantly (75%; 6/8) in association with ETV6::RUNX1 fusion. A higher proportion of measurable residual disease (MRD) positivity occurred on day 33 and day 78 in the presence of IKZF1 deletion (day 33: 50% vs 24%; day 78: 36% vs 7%) and in patients with BCR::ABL1-like features (day 33: 69% vs 25%; day 78: 50% vs 13%). Three-year event-free survival of B-ALL patients who tested MRD negative on day 33 was notably shorter in the presence of TP53 (p=0.002) and CREBBP mutation (p=0.007), compared to wild type cases.
Conclusions: Our dataset offers unique insights into the genomic and transcriptomic landscape of children with ALL, unveiling novel gene fusions and previously unknown relationships between disease prognosis and TP53 and CREBBP mutations in this real-world cohort.
Funding: FK20_134253 K21_137948 H2020-739593 EFOP-3.6.3-VEKOP-16-2017-00009 KDP-2020-1008491 TKP2021-EGA-24 TKP2021-NVA-15

University

Semmelweis University

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

16:10

End

16:13