Advances in Myeloproliferative Neoplasms by single-cell omics studies

Myeloproliferative neoplasms (MPNs) are clonal hematologic malignancies driven by somatic mutations in JAK2, CALR, or MPL, yet exhibit substantial biological and clinical heterogeneity. Early insights into MPN clonal architecture were derived from single-cell-derived colony assays, which enabled reconstruction of mutation timing and order but were limited by low throughput and ex vivo conditions. Advances in single-cell omics technologies have transformed MPN research by enabling high-resolution analysis of genetic, transcriptional, and epigenetic heterogeneity. Studies from modified single cell RNA sequencing approaches such as Target-seq, and Genotyping of Transcriptomes (GoT) revealed that driver mutations promote lineage bias and increased proliferation of mutant progenitors while largely preserving the overall hematopoietic hierarchy. Single cell RNA sequencing has also provided important insights into mechanisms of treatment resistance and disease progression. Similarly, sing-cell ATAC sequencing has corroborated many findings from single-cell RAN sequencing and also discovered alterations in chromatin accessibility and regulatory pathways that are not captured by single-cell transcriptomic analysis. By integrating colony-based and modern single-cell approaches, this review provides a framework for understanding MPN evolution and its implications for disease biology and therapy.