AUTHOR=Sol Ruiz María , Sosa Ezequiel , Avendaño Daniel , Gomez Mercado Ignacio , Lacreu María Laura , Riccheri Cecilia , Schuttenberg Virginia , Aversa Luis , Vazquez Elba , Gueron Geraldine , Cotignola Javier 

TITLE=Genetic characterization of pediatric B-cell acute lymphoblastic leukemia in Argentina uncovers molecular heterogeneity and novel variants

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1701680

DOI=10.3389/fphar.2025.1701680

ISSN=1663-9812

ABSTRACT=IntroductionAcute lymphoblastic leukemia is the most common childhood cancer, yet its diagnosis and risk classification remain incomplete in many regions due to limited access to molecular studies.MethodsWe present the first comprehensive genetic and molecular characterization of childhood B-cell Acute lymphoblastic leukemia in Argentina using whole-transcriptome sequencing of diagnostic bone marrow samples from 32 patients enrolled in the international clinical protocol ALLIC-BFM-2009.ResultsBy integrating publicly available bioinformatic tools, we achieved molecular subtyping in over 93% of cases, a significant increase from the 31% rate attained through traditional methods. Our analysis revealed a diverse landscape of known and novel genetic alterations, including gene fusions, single nucleotide variants, and gene expression signatures relevant to prognosis and therapy. Importantly, we identified novel single nucleotide variants in DUX4, CSF3R and CREBBP, and fusion transcripts.DiscussionThis study not only reports transcriptional heterogeneity in our Latin American cohort but also supports the implementation of open-source bioinformatic pipelines in resource-limited settings to enhance precision diagnosis and guide personalized treatment.