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Blood, 15 May 2008, Vol. 111, No. 10, pp. 5109-5117.
Prepublished online as a Blood First Edition Paper on March 11, 2008; DOI 10.1182/blood-2007-05-091579.
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NEOPLASIA
Transgenic expression of JAK2V617F causes myeloproliferative disorders in mice
Shu Xing1,2,
Tina Ho Wanting1,
Wanming Zhao1,2,
Junfeng Ma1,2,
Shaofeng Wang1,2,
Xuesong Xu2,3,
Qingshan Li2,
Xueqi Fu2,
Mingjiang Xu4, and
Zhizhuang Joe Zhao1,2
1 Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City;
2 Edmond H. Fischer Signal Transduction Laboratory, College of Life Sciences, and
3 Clinical Laboratory, China Japan Union Hospital, Jilin University, Changchun, China; and
4 Division of Hematology/Oncology, Mount Sinai School of Medicine, New York, NY
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.
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