High-Throughput Sequencing Revealing BCR and TCR Repertoires as Potential Prognostic Biomarkers for Pediatric Patients with B-ALL

Abstract

Background: B-ALL is a hematologic malignancy that recurs in approximately 10-20% of children and has a poor prognosis. New prognostic biomarkers are needed to improve individualized therapy and achieve better clinical outcomes. Methods: In this study, high-throughput sequencing technology was used to detect the BCR and TCR repertoires in children with B-ALL. Results: We observed a gradual increase in the diversity of the BCR and TCR repertoires during the developmental stages (Pro-, Common-, Pre-B-ALL) of precursor B-ALL cells. Conversely, as minimal residual disease (MRD) levels on day 19 of induction therapy increased, the BCR/TCR repertoire diversity decreased. Furthermore, the BCR/TCR repertoire diversity was significantly greater in B-ALL patients at low risk and those harboring the ETV6/RUNX1 fusion than in patients with medium-risk disease and those harboring the ZNF384 fusion. Notably, the abundance of BCR/TCR clones varied significantly among patients with B-ALL and different clinical characteristics. Specifically, patients with Pre-B-ALL, low-risk disease, D19MRD levels <1%, and harboring the ETV6/RUNX1 fusion exhibited a predominance of BCR/TCR small clones. In our study, we noted an imbalanced occurrence of V and J gene utilization among patients with BALL; however, there seemed to be no discernible correlation with the clinical attributes. Conclusion: BCR/TCR repertoires are expected to be potential prognostic biomarkers for patients with B-ALL.