RNA-seq from bone marrow samples of pediatric acute lymphoblastic leukemia patients at diagnosis

Pediatric acute lymphoblastic leukemia (ALL) is highly heterogeneous at the molecular level, with more than 20 molecular subtypes identified so far in B-ALL that are the basis for risk-adapted therapy and precision medicine. They are characterized by specific chromosomal rearrangements, gene expression profiles, aneuploidies and point mutations, and their identification relies on the technical availability in each center. In this context, increasing complexity of molecular classification implies technical, analytical and economic challenges that together limit their implementation, especially in low and middle income countries. In this work we applied transcriptome sequencing for molecular classification of B-ALL at diagnosis in pediatric patients from the multicentric ALLIC-GATLA-2010 clinical protocol in Argentina. By combining multiple bioinformatic tools, we successfully identified single nucleotide variants, fusion transcripts and gene expression profiles, achieving molecular classification of more than 90% of patients. We could also detect high-risk molecular features and novel genetic alterations. Results obtained in this work could be of clinical utility to improve risk stratification and identify therapeutic targets, especially in patients that currently result unclassified by traditional diagnostic techniques.