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Blood, 1 June 2006, Vol. 107, No. 11, pp. 4274-4281. Prepublished online as a Blood First Edition Paper on February 14, 2006; DOI 10.1182/blood-2005-12-4824. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-12-4824v1 107/11/4274    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wernig, G. Articles by Gilliland, D G Search for Related Content PubMed PubMed Citation Articles by Wernig, G. Articles by Gilliland, D G Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 6, 2005 Accepted January 20, 2006 Expression of Jak2V617F causes a polycythemia vera-like disease with associated myelofibrosis in a murine bone marrow transplant model Gerlinde Wernig, Thomas Mercher, Rachel Okabe, Ross L Levine, Benjamin H Lee, and D G Gilliland* Division of Hematology, Department of Medicine, Harvard Medical School, Boston, MA, USA Division of Hematology, Department of Medicine, Harvard Medical School, Boston, MA, USA; Department of Medical Oncology, Dana-Faber Cancer Institute, Harvard Medical School, Boston, MA, USA Division of Hematology, Department of Medicine, Harvard Medical School, Boston, MA, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA Division of Hematology, Department of Medicine, Harvard Medical School, Boston, MA, USA; Howard Hughes Medical Institute, Boston, MA, USA * Corresponding author; email: ggilliland{at}rics.bwh.harvard.edu. An acquired somatic mutation, Jak2V617F, was recently discovered in the majority of patients with polycythemia vera (PV), chronic idiopathic myelofibrosis (CIMF) and essential thrombocythemia (ET). To investigate the role of this mutation in vivo we transplanted bone marrow (BM) transduced with a retrovirus expressing either Jak2 wildtype (wt) or Jak2V617F into lethally irradiated syngeneic recipient mice. Expression of Jak2V617F, but not Jak2wt resulted in clinico-pathological features that closely resembled PV in humans. These included striking elevation in hemoglobin/hematocrit, leukocytosis, megakaryocyte hyperplasia, extramedullary hematopoiesis resulting in splenomegaly, and reticulin fibrosis in the bone marrow. Histopathology and flow cytometric analysis showed an increase in maturing myeloid lineage progenitors, although megakaryocytes showed decreased polyploidization and staining for acetylcholinesterase. In vitro analysis of primary cells showed constitutive activation of Stat5 and cytokine independent growth of CFU-e and erythropoietin hypersensitivity, and Southern blot for retroviral integration indicated that the disease was oligoclonal. Furthermore, we observed strain-specific differences in phenotype with Balb/C mice demonstrating markedly elevated leukocyte counts, splenomegaly and reticulin fibrosis when compared with C57Bl/6 mice. We conclude that expression of Jak2V617F in bone marrow progenitors results in a PV-like syndrome with myelofibrosis, and that there are strain specific modifiers that may in part explain phenotypic pleiotropy of Jak2V617F-associated myeloproliferative disease in humans. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. C.C. Liu, E. Caulder, J. Li, P. Waeltz, A. Margulis, R. Wynn, M. Becker-Pasha, Y. Li, E. Crowgey, G. Hollis, et al. 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