Hypothetical model of the different biology of MPN development and progression between women and men. Men may have higher genomic instability in their primitive cell compartment and a potentially more inflammatory microenvironment, causing the increased allele burden of their MPN-specific mutation. These characteristics can also induce the acquisition of additional non–MPN-specific somatic mutations, rendering the disease less dependent on the MPN-specific mutation and promoting the development of clonal hematopoiesis, MDS/MPN, or MF phenotype, accelerated disease progression, and worse survival.