| First Author | Dutta A | Year | 2017 |
| Journal | Blood | Volume | 130 |
| Issue | 7 | Pages | 920-932 |
| PubMed ID | 28637665 | Mgi Jnum | J:244956 |
| Mgi Id | MGI:5913735 | Doi | 10.1182/blood-2016-12-757344 |
| Citation | Dutta A, et al. (2017) Hmga2 promotes the development of myelofibrosis in Jak2V617F knockin mice by enhancing TGF-beta1 and Cxcl12 pathways. Blood 130(7):920-932 |
| abstractText | Myelofibrosis (MF) is a devastating blood disorder. The JAK2V617F mutation has been detected in approximately 50% cases of MF. Elevated expression of high-mobility group AT hook 2 (HMGA2) has also been frequently observed in patients with MF. Interestingly, upregulation of HMGA2 expression has been found in association with the JAK2V617F mutation in significant cases of MF. However, the contribution of HMGA2 in the pathogenesis of MF remains elusive. To determine the effects of concurrent expression of HMGA2 and JAK2V617F mutation in hematopoiesis, we transduced bone marrow cells from Jak2V617F knockin mice with lentivirus expressing Hmga2 and performed bone marrow transplantation. Expression of Hmga2 enhanced megakaryopoiesis, increased extramedullary hematopoiesis, and accelerated the development of MF in mice expressing Jak2V617F Mechanistically, the data show that expression of Hmga2 enhances the activation of transforming growth factor-beta1 (TGF-beta1) and Cxcl12 pathways in mice expressing Jak2V617F In addition, expression of Hmga2 causes upregulation of Fzd2, Ifi27l2a, and TGF-beta receptor 2. Forced expression of Cxcl12, Fzd2, or Ifi27l2a increases megakaryocytic differentiation and proliferation in the bone marrow of Jak2V617F mice, whereas TGF-beta1 or Cxcl12 stimulation induces collagen deposition in the bone marrow mesenchymal stromal cells. Together, these findings demonstrate that expression of Hmga2 cooperates with Jak2V617F in the pathogenesis of MF. |
