Development of ET, primary myelofibrosis and PV in mice expressing JAK2 V617F
| Autor: | Takashi Kumano, Takuro Kameda, Kotaro Shide, Satoru Hasuike, Kouichi Ohshima, Youko Kubuki, Hiroo Abe, Kazunori Kusumoto, Kenji Nagata, Tadashi Matsuda, Haruko Shimoda, Keiko Katayose, Kennosuke Karube, Kazuya Shimoda, Katsuto Takenaka, Yoshihiro Tahara, Seido Oku, Mine Harada |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Pathology Leukocytosis Anemia Mice Transgenic Biology Mice Polycythemia vera hemic and lymphatic diseases Internal medicine STAT5 Transcription Factor medicine Animals Humans Myeloid Cells RNA Messenger Phosphorylation Myelofibrosis Polycythemia Vera Bone Marrow Transplantation Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Hematology Essential thrombocythemia Granulocytosis Janus Kinase 2 medicine.disease medicine.anatomical_structure Gene Expression Regulation Oncology Primary Myelofibrosis Mutation Cancer research Cytokines Female Bone marrow medicine.symptom Megakaryocytes Proto-Oncogene Proteins c-akt Thrombocythemia Essential |
| Zdroj: | Leukemia. 22:87-95 |
| ISSN: | 1476-5551 0887-6924 |
| DOI: | 10.1038/sj.leu.2405043 |
| Popis: | An acquired JAK2 V617F mutation is found in most patients with polycythemia vera (PV), and about half of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). Mice transplanted with bone marrow cells in which JAK2 V617F was retrovirally expressed developed PV-like features, but not ET or PMF. To address the contribution of this mutation to the pathogenesis of these three MPDs, we generated two lines of JAK2 V617F transgenic mice. One line showed granulocytosis after 4 months of age. Among 43 mice, 8 (19%) showed polycythemia and 15 (35%) showed thrombocythemia. The second line showed extreme leukocytosis and thromobocytosis. They showed anemia that means Hb value from 9 to 10 g per 100 ml when 1 month old. Myeloid cells and megakaryocytes were predominant in the bone marrow of these animals, and splenomegaly was observed. The expression of JAK2 V617F mRNA in bone marrow cells was 0.45 and 1.35 that of endogenous wild-type JAK2 in the two lines, respectively. In vitro analysis of bone marrow cells from both lines showed constitutive activation of ERK1/2, STAT5 and AKT, and augmentation of their phosphorylations by cytokine stimulation. We conclude that in vivo expression of JAK2 V617F results in ET-, PMF- and PV-like disease. |
| Databáze: | OpenAIRE |
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