2012 Volume 58 Issue 3 Pages 441-447
Myeloproliferative neoplasms (MPNs), which include polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are characterized by clonal proliferative hematopoiesis with increased blood cell count. MPNs are slowly progressive, but are frequently complicated by myelodysplastic syndromes or secondary myelofibrosis with poor outcome due to transfusion dependence and leukemic transformation. Recently, several genetic abnormalities, such as JAK2 and TET2 or polycomb group genes, involved in cell proliferation and epigenetic regulation, respectively, have been reported in patients with MPN. In addition, overexpression and rearrangement of HMGA2, which plays important roles in cell proliferation and differentiation, have been shown in patients with MPNs and related disorders. In these patients, chromosomal rearrangement often removes the 3' untranslated region (UTR) of HMGA2, which contains specific sites for let-7 micro RNAs, which regulate expression of HMGA2. Therefore, we produced transgenic mice overexpressing HMGA2 without its 3'UTR, which revealed a proliferative hematopoiesis mimicking MPN and expansion of hematopoietic cells at the level of the hematopoietic stem cell. Thus, HMGA2 may play a role in the pathogenesis of MPN, together with other reported genes.
