Transgenic expression of JAK2V617F causes myeloproliferative disorders in mice
Open Access
- 15 May 2008
- journal article
- Published by American Society of Hematology in Blood
- Vol. 111 (10), 5109-5117
- https://doi.org/10.1182/blood-2007-05-091579
Abstract
The JAK2V617F mutation was found in most patients with myeloproliferative disorders (MPDs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. We have generated transgenic mice expressing the mutated enzyme in the hematopoietic system driven by a vav gene promoter. The mice are viable and fertile. One line of the transgenic mice, which expressed a lower level of JAK2V617F, showed moderate elevations of blood cell counts, whereas another line with a higher level of JAK2V617F expression displayed marked increases in blood counts and developed phenotypes that closely resembled human essential thrombocythemia and polycythemia vera. The latter line of mice also developed primary myelofibrosis-like symptoms as they aged. The transgenic mice showed erythroid, megakaryocytic, and granulocytic hyperplasia in the bone marrow and spleen, displayed splenomegaly, and had reduced levels of plasma erythropoietin and thrombopoietin. They possessed an increased number of hematopoietic progenitor cells in peripheral blood, spleen, and bone marrow, and these cells formed autonomous colonies in the absence of growth factors and cytokines. The data show that JAK2V617F can cause MPDs in mice. Our study thus provides a mouse model to study the pathologic role of JAK2V617F and to develop treatment for MPDs.This publication has 31 references indexed in Scilit:
- Characterization of a Highly effective protein substrate for analysis of JAK2V617F ActivityExperimental Hematology, 2007
- In vitro expansion of erythroid progenitors from polycythemia vera patients leads to decrease in JAK2V617F alleleExperimental Hematology, 2007
- Erlotinib Effectively Inhibits JAK2V617F Activity and Polycythemia Vera Cell GrowthOnline Journal of Public Health Informatics, 2007
- Polycythemia vera is not initiated by JAK2V617F mutationExperimental Hematology, 2007
- Molecular Pathogenesis and Therapy of Polycythemia Induced in Mice by JAK2 V617FPLOS ONE, 2006
- The Myeloproliferative DisordersThe New England Journal of Medicine, 2006
- JAK2V617F: prevalence in a large Chinese hospital populationBlood, 2006
- The V617F JAK2 mutation is uncommon in cancers and in myeloid malignancies other than the classic myeloproliferative disordersBlood, 2005
- A Gain-of-Function Mutation ofJAK2in Myeloproliferative DisordersThe New England Journal of Medicine, 2005
- A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia veraNature, 2005