Integrative transcriptomic profiling reveals convergent coding and non-coding signatures in pediatric bone marrow failure syndromes

Abstract

Abstract Pediatric bone marrow failure (BMF) comprises heterogeneous inherited and immune-mediated disorders, yet many cases remain genetically unclassified despite comprehensive genomic evaluation. To identify shared transcriptional features beyond protein-coding variation, we performed total RNA sequencing on bone marrow samples from pediatric BMF patients (n=12) and controls (n=2). Based on whole-genome sequencing, patients were stratified into genetically defined BMF (g-BMF, n=4) and genetically undefined BMF (u-BMF, n=8). Comparative transcriptomic analyses revealed minimal differences in protein-coding genes and long non-coding RNAs (lncRNAs) between g-BMF and u-BMF, indicating strong transcriptional concordance. Compared with controls, 55.2% of differentially expressed protein-coding genes were shared between g-BMF and u-BMF and were predominantly upregulated. Pathway enrichment analyses consistently identified immune activation and cellular stress-response pathways, suggesting a shared inflammatory transcriptional state across pediatric BMF irrespective of genetic classification. LncRNA profiling showed that 69.6% of differentially expressed lncRNAs were common to both BMF groups. ATP1A1-AS1, USP3-AS1 , and SNHG32 were reproducibly overexpressed and validated by RT–qPCR. Correlation-based pathway analyses associated ATP1A1-AS1 and USP3-AS1 with immune-related and biosynthetic programs, whereas SNHG32 showed a distinct co-expression pattern. Collectively, these findings indicate shared coding and non-coding transcriptional features in pediatric BMF that appear largely independent of genetic classification.