Identification of Novel Fusion Genes in Pediatric B-ALL patients Using Whole Transcriptome Sequencing

Background: Fusion genes (FGs), serving as diagnostic, prognostic, and therapeutic markers, are key molecular aberrations in acute leukemia. They are also essential for risk stratification and measurable residual disease (MRD) monitoring. This study aimed to characterize the distribution of FGs using whole transcriptome sequencing (WTS). Materials and Methods: A total of 12 newly diagnosed treatment naive pediatric BALL cases from a local tertiary care hospital were enrolled in this study. Following the nucleic acids isolation procedures, the RNA sequencing was done for 12 BALL patients to find the fusion genes. Results: In the present cohort of 12 pediatric BALL patients, 19 high-confidence in-frame gene fusion events were identified involving 29 unique partner genes. The commonly reported sub-type defining rearrangements in BALL , including ETV6-RUNX1, TCF3-PBX1 and BCR-ABL1, were found in 8.3 % of the patients whereas the rearrangements in commonly prevalent genes in BALL like PAX5, ABL1 and ATXN3 were also found in 8.3 % of the patients with different unreported partner genes but reported earlier in various studies i.e. PAX-ETV6 (8.3%), ABL1-SNX2 (8.3%) and CMC2-ATXN3. Conclusion: The present work expands the scope of fusions in pediatric BALL by revealing unreported and domain-retaining fusions, as well as co-occurring rearranged fusions with possible combinatorial outcomes. By introducing WTS into clinical workflows, the genetic classification can be done more accurately and new pathogenic drivers missed by traditional methods can be identified, highlighting the increased significance of transcriptomic profiling in the diagnosis, prognosis, and personalized therapy of leukemia.