Emerging applications of long-read sequencing in hematological malignancies: highlights from the 2025 ASH annual...

Long-read sequencing (LRS) is rapidly advancing and demonstrates considerable promise in hematological malignancies. At the 2025 ASH meeting, numerous studies highlighted advances in applying LRS across diverse hematological malignancies. Rapid LRS-based whole-genome sequencing and adaptive sampling enable real-time subtype assignment, detection of SNVs, CNVs, and gene fusions, as well as methylation-based classification. By spanning repetitive and structurally complex regions, LRS enhances genetic subtyping and uncovers clinically relevant structural variants often missed by short-read technologies. Full-length and single-cell RNA sequencing further resolve isoforms, splicing programs, and fusion transcripts within their clonal contexts, supporting precision therapy and refined risk stratification. As accuracy improves and costs decline, LRS is poised for broader integration into routine clinical diagnostics.