Philadelphia chromosome-negative myeloproliferative neoplasms (MPN), which include polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are characterized by clonal proliferative hematopoiesis with increased blood cell count. Clonal expansion mechanisms in MPN and related disorders such as myelodysplastic syndromes (MDS) remain to be elucidated. Although mutations in the JAK2 gene lead to a proliferative hematopoiesis in majority of MPN and some MDS, the mutation alone does not cause a clonal expansion. In addition to JAK2 mutations, several genetic abnormalities, including TET2 and polycomb group genes involving epigenetic regulation have been reported in patients with MPN. Moreover, overexpression of HMGA2 due to removal of specific sites in its 3' untranslated region for regulatory let-7 micro RNAs may contribute to the proliferative hematopoiesis with conferring a growth advantage at the level of a hematopoietic stem cell in some cases with MPN.