Development of ET, primary myelofibrosis and PV in mice expressing JAK2 V617F

K. Shide, H. K. Shimoda, T. Kumano, K. Karube, T. Kameda, Katsuto Takenaka, S. Oku, H. Abe, K. S. Katayose, Y. Kubuki, K. Kusumoto, S. Hasuike, Y. Tahara, K. Nagata, T. Matsuda, K. Ohshima, M. Harada, K. Shimoda

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Abstract

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 10g per 100ml 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.

Original languageEnglish
Pages (from-to)87-95
Number of pages9
JournalLeukemia
Volume22
Issue number1
DOIs
Publication statusPublished - Jan 1 2008

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Essential Thrombocythemia
Polycythemia Vera
Primary Myelofibrosis
Bone Marrow Cells
Thrombocytosis
Polycythemia
Mutation
Megakaryocytes
Splenomegaly
Leukocytosis
Myeloid Cells
Transgenic Mice
Anemia
Bone Marrow
Phosphorylation
Cytokines
Cell Line
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Shide, K., Shimoda, H. K., Kumano, T., Karube, K., Kameda, T., Takenaka, K., ... Shimoda, K. (2008). Development of ET, primary myelofibrosis and PV in mice expressing JAK2 V617F. Leukemia, 22(1), 87-95. https://doi.org/10.1038/sj.leu.2405043

Development of ET, primary myelofibrosis and PV in mice expressing JAK2 V617F. / Shide, K.; Shimoda, H. K.; Kumano, T.; Karube, K.; Kameda, T.; Takenaka, Katsuto; Oku, S.; Abe, H.; Katayose, K. S.; Kubuki, Y.; Kusumoto, K.; Hasuike, S.; Tahara, Y.; Nagata, K.; Matsuda, T.; Ohshima, K.; Harada, M.; Shimoda, K.

In: Leukemia, Vol. 22, No. 1, 01.01.2008, p. 87-95.

Research output: Contribution to journalArticle

Shide, K, Shimoda, HK, Kumano, T, Karube, K, Kameda, T, Takenaka, K, Oku, S, Abe, H, Katayose, KS, Kubuki, Y, Kusumoto, K, Hasuike, S, Tahara, Y, Nagata, K, Matsuda, T, Ohshima, K, Harada, M & Shimoda, K 2008, 'Development of ET, primary myelofibrosis and PV in mice expressing JAK2 V617F', Leukemia, vol. 22, no. 1, pp. 87-95. https://doi.org/10.1038/sj.leu.2405043
Shide K, Shimoda HK, Kumano T, Karube K, Kameda T, Takenaka K et al. Development of ET, primary myelofibrosis and PV in mice expressing JAK2 V617F. Leukemia. 2008 Jan 1;22(1):87-95. https://doi.org/10.1038/sj.leu.2405043
Shide, K. ; Shimoda, H. K. ; Kumano, T. ; Karube, K. ; Kameda, T. ; Takenaka, Katsuto ; Oku, S. ; Abe, H. ; Katayose, K. S. ; Kubuki, Y. ; Kusumoto, K. ; Hasuike, S. ; Tahara, Y. ; Nagata, K. ; Matsuda, T. ; Ohshima, K. ; Harada, M. ; Shimoda, K. / Development of ET, primary myelofibrosis and PV in mice expressing JAK2 V617F. In: Leukemia. 2008 ; Vol. 22, No. 1. pp. 87-95.
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AU - Kameda, T.

AU - Takenaka, Katsuto

AU - Oku, S.

AU - Abe, H.

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AU - Kusumoto, K.

AU - Hasuike, S.

AU - Tahara, Y.

AU - Nagata, K.

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AU - Harada, M.

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