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

BackgroundFusion 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 MethodsA total of 12 newly diagnosed treatment naive pediatric B-ALL 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 B-ALL patients to find the fusion genes. ResultsIn the present cohort of 12 pediatric B-ALL patients, 19 high-confidence in-frame gene fusion events were identified involving 29 unique partner genes. The commonly reported sub-type defining rearrangements in B-ALL, including ETV6-RUNX1, TCF3-PBX1 and BCR-ABL1, were found in 8.3 % of the patients whereas the rearrangements in commonly prevalent genes in B-ALL 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. ConclusionThe present work expands the scope of fusions in pediatric B-ALL 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.