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Myeloproliferative neoplasms (MPN) are a group of clonal, stem cell derived hematopoietic malignancies driven by aberrant JAK/STAT signalling. Although they are genetically simple diseases, MPNs are phenotypically heterogeneous, reflecting underlying intra-tumoral heterogeneity driven by the interplay of genetic and non-genetic factors. As their evolution is determined by factors that enable certain cellular subsets to outcompete others, techniques that resolve cellular heterogeneity at the single-cell level are ideally placed to provide new insights into MPN biology. With these insights comes the potential to uncover new approaches to predict the clinical course and treat these cancers, ultimately improving outcomes for patients. MPNs present a particularly tractable model of cancer evolution, as most patients present in an early disease phase and only a small proportion progress to aggressive disease. Therefore, it is not surprising that many of the groundbreaking technological advances in single-cell omics have been pioneered by their application in MPNs. In this review article, we explore how single-cell approaches have provided transformative insights into MPN disease biology, that are broadly applicable across human cancers, and discuss how these studies might be swiftly translated into clinical pathways and may eventually underpin precision medicine.

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