TY  - JOUR
N2  - Risk-adapted treatment protocols conferred remarkable improvement in the survival rates of pediatric acute lymphoblastic leukemia/lymphoma (ALL/LBL). Nevertheless, clinical management is still challenging in certain molecular subgroups and in the presence of alterations associated with an increased rate of relapse. In this study, disease-relevant genomic and transcriptomic profiles were established in a prospective, multicenter, real-world cohort involving 192 children diagnosed with ALL/LBL. Gene fusions were detected in 34.9% of B-ALL and 46.4% of T-ALL patients, with novel chimeric genes involving JAK2, KMT2A, PAX5, RUNX1 and NOTCH1, and with KMT2A-rearranged patients displaying the worst 3-year event-free survival (p=0.019). Non-synonymous mutations were uncovered in 74.9% of the analyzed patients, and a pairwise scrutiny of genetic lesions revealed recurrent clonal selection mechanisms commonly converging on the same pathway (e.g. Ras, JAK/STAT and Notch) in individual patients. Investigation of matched diagnostic and relapse samples unraveled complex subclonal variegation, and mutations affecting the NT5C2, TP53, CDKN2A, and PIK3R1 genes, emerging at the time of relapse. TP53 and CREBBP mutations, even as subclonal aberrations, were associated with shorter 3-year event-free survival among all patients with B-ALL (TP53 mutant vs wild-type: p=0.008, CREBBP mutant vs wild-type: p=0.010); and notably, B-ALL patients showing no measurable residual disease on day 33 could be further stratified based on TP53 mutational status (p<0.001). Our in-depth molecular characterization performed across all risk groups identified novel opportunities for molecularly targeted therapy in 55.9% of high-risk and in 31.6% of standard/intermediate-risk patients.
UR  - https://doi.org/10.1016/j.modpat.2025.100741
JF  - MODERN PATHOLOGY
TI  - Molecular profiling reveals novel gene fusions and genetic markers for refined patient stratification in pediatric acute lymphoblastic leukemia
IS  - 6
EP  - 14
VL  - 38
SN  - 0893-3952
N1  - * Megosztott szerz?ség
ID  - publicatio36296
AV  - public
Y1  - 2025///
A1  -  Péterffy Borbála
A1  -  Krizsán Szilvia
A1  -  Egyed Bálint
A1  -  Bedics Gábor
A1  -  Benard-Slagter Anne
A1  -  Palit Sander
A1  -  Erdélyi Dániel
A1  -  Müller Judit
A1  -  Nagy Tibor
A1  -  Hegyi Lajos
A1  -  Bek? Anna
A1  -  Kenéz Lili Anna
A1  -  Jakab Zsuzsanna
A1  -  Péter György
A1  -  Zombori Marianna
A1  -  Csanádi Krisztina
A1  -  Ottóffy Gábor
A1  -  Csernus Katalin
A1  -  Vojcek Ágnes
A1  -  Tiszlavicz Lilla Györgyi
A1  -  Gábor Krisztina
A1  -  Kelemen Ágnes
A1  -  Hauser Péter
A1  -  Kállay Krisztián
A1  -  Kertész Gabriella
A1  -  Gaál Zsuzsanna
A1  -  Szegedi István
A1  -  Barna Gábor
A1  -  Márk Ágnes
A1  -  Haltrich Irén
A1  -  Hevessy Zsuzsanna
A1  -  Ujfalusi Anikó
A1  -  Kajtár Béla
A1  -  Timár Botond
A1  -  Kiss Csongor
A1  -  Kriván Gergely
A1  -  Matolcsy András
A1  -  Savola Suvi
A1  -  Kovács Gábor
A1  -  Bödör Csaba
A1  -  Alpár Donát
ER  -