Constitutional variation in genes that can influence the MPN onset can be distinguished in two categories: (1) mutations that occur in the whole population and are responsible for a small increase in MPN, and (2) familial mutations with high penetrance that can increase the risk from 1.5 to 3 of MPN development, like TERT or the JAK2 46/1 haplotype [42]. This evidence concerns the gene JAK2 and myeloproliferative disorder.