The “hypermutability hypothesis” derives from the observation that MPN patients heterozygous for the haplotypeGGCC_46/1 preferentially acquire the V617F mutation in cis with the GGCC predisposition allele [7,8,9]; this germline haplotype may somehow determine an increase in the mutation rate at the JAK2 locus and those mutations that confer a selective advantage, such as JAK2 V617F, would cause a clonal myeloproliferative disorder [9,62]. This evidence concerns the gene JAK2 and myeloproliferative neoplasm.