Figure 1. The transcriptomic signature of circulating platelets provides a window into disease biology in MPNs.

Megakaryocytes are expanded in MPNs and comprise a mixture of wild-type cells and cells with driver mutations and sub-clones with additional mutations, reflecting the heterogeneity within the HSC pool from which they are derived. Megakaryocytes influence surrounding cells in the bone marrow niche through non-cell-autonomous effects and are themselves influenced by environmental factors including inflammation and fibrosis. As well as reflecting the status of the megakaryocyte at the time of platelet release into the circulation, the platelet transcriptome is further influenced by inter-cellular transfer of RNA and by splicing events triggered by receptor activation. The transcriptome therefore gives insights into disease biology and carries signatures that distinguish between disease types and stages of disease progression.