Distribution of molecular subtypes in a Colombian cohort of patients with acute lymphoblastic leukemia using whole-transcriptome analysis

Introduction Acute lymphoblastic leukemia (ALL) is a common pediatric malignancy and shows marked genetic heterogeneity. Transcriptomic profiling may improve molecular diagnosis and risk stratification, particularly in admixed Latin American populations. Methods We characterized the transcriptomic landscape of pediatric ALL in 40 Colombian patients aged <20 years using whole-transcriptome RNA sequencing of diagnostic bone marrow or peripheral blood samples. Bioinformatic analyses enabled molecular subtype assignment, fusion detection, differential expression analysis, and variant calling. Results The median age was 8 years, and 8 patients had measurable residual disease at the end of induction. The most frequent subtypes were ETV6::RUNX1 and Ph-like, each representing 15% of cases. Fusions, including MEF2D::HNRNPUL1 and SEPTIN9::ABL1 , were identified. Differential expression analysis revealed 3,864 genes distinguishing ALL from non-leukemic controls, with enrichment of hematologic malignancy, B-cell differentiation, immune, and inflammatory pathways. Conclusions Molecular classification refined conventional risk stratification in 10% of patients, supporting the potential clinical utility of transcriptomic profiling in pediatric ALL.