The first two conundrums are easily solved, since the three different MPN driver mutations activate the same essential tyrosine kinase for hematopoiesis, JAK2, albeit by different mechanisms, while the phenotypic expression of a specific MPN is not dictated entirely by an MPN driver mutation, but by the host genetic variation, of which sex and age are the most important factors [1]. This evidence concerns the gene JAK2 and myeloproliferative disorder.