A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera.

@article{James2005AUC,
  title={A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera.},
  author={C. James and V. Ugo and J. L. Le Cou{\'e}dic and J. Staerk and F. Delhommeau and C. Lacout and L. Garçon and H. Raslova and R. Berger and A. Bennaceur-Griscelli and J. Villeval and S. Constantinescu and N. Casadevall and W. Vainchenker},
  journal={Nature},
  year={2005},
  volume={434 7037},
  pages={
          1144-8
        }
}
Myeloproliferative disorders are clonal haematopoietic stem cell malignancies characterized by independency or hypersensitivity of haematopoietic progenitors to numerous cytokines. The molecular basis of most myeloproliferative disorders is unknown. On the basis of the model of chronic myeloid leukaemia, it is expected that a constitutive tyrosine kinase activity could be at the origin of these diseases. Polycythaemia vera is an acquired myeloproliferative disorder, characterized by the… Expand

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References

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A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera
TLDR
A clonal and recurrent mutation in the JH2 pseudo-kinase domain of the Janus kinase 2 (JAK2) gene in most (> 80%) polycythaemia vera patients leads to constitutive tyrosine phosphorylation activity that promotes cytokine hypersensitivity and induces erythrocytosis in a mouse model. Expand
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A single acquired mutation of JAK2 was noted in more than half of patients with a myeloproliferative disorder and its presence in all erythropoietin-independent erythroid colonies demonstrates a link with growth factor hypersensitivity, a key biological feature of these disorders. Expand
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A gain-of-function mutation of JAK2 may explain the hypersensitivity of PV progenitor cells to growth factors and cytokines and is defined as a molecular defect of PV. Expand
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Genetic evidence and in vitro functional studies indicate that V617F gives hematopoietic precursors proliferative and survival advantages and a high proportion of patients with myeloproliferative disorders carry a dominant gain-of-function mutation of JAK2. Expand
Multiple signaling pathways are involved in erythropoietin-independent differentiation of erythroid progenitors in polycythemia vera.
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TLDR
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TLDR
Functional analysis demonstrates that this mutation confers erythropoietin-independent growth in vitro, deregulates signaling pathways downstream of JAK2, and causes polycythemia in mice, and identifies a new molecular target for drug discovery. Expand
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TLDR
The drug has now been shown to display equally impressive therapeutic activity in eosinophilia-associated chronic myeloproliferative disorders that are characterized by activating mutations of either the PDGFRB or the PDGFRA gene. Expand
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