Landscape of circular RNAs in acute myeloid leukemia and their clinical significance.

Circular RNAs (circRNAs) have emerged as important regulators in cancer biology, but their roles in acute myeloid leukemia (AML) remain poorly characterized due to limited sample sizes and technical challenges in RNA sequencing. Here, we analyze RNA-sequencing data from 315 Swedish AML patients to create the most comprehensive circRNA profile in AML to date. We identify 5,711 high-confidence circRNAs across 315 AML samples, including 402 differentially expressed between AML and healthy controls, with host genes enriched in hematopoietic pathways. We further discover two circRNAs including hsa_circ_0024048 (p = 2.16×10⁻⁶, FDR = 0.012) and hsa_circ_0084678 (p = 1.33×10⁻⁵, FDR = 0.075) whose high expression is associated with significantly improved overall survival, a relationship not observed in their respective host genes. Furthermore, these circRNAs are associated with sensitivities of several drugs, as validated in external datasets (p < 0.05). We identify 451 circRNAs with ELN2022 risk group-specific expression patterns, highlighting circRNA heterogeneity. Subtype analysis further reveals that hsa_circ_0080850 is specifically associated with worse survival (p = 2.13×10⁻ and lower remission rates (38.9% vs 74.7%) within the ELN2022 Favorable subgroup. To conclude, this study establishes the most comprehensive circRNA landscape in AML to date and demonstrates their potential as biomarkers and therapeutic targets, suggesting further investigation into circRNA-driven precision medicine in AML.