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={Chlo{\'e} James and Val{\'e}rie Ugo and Jean Pierre Le Cou{\'e}dic and Judith Staerk and François Delhommeau and Catherine Lacout and Lo{\"i}c Garçon and Hana Raslova and Roland Berger and Annelise Bennaceur-Griscelli and Jean Luc Villeval and Stefan N. Constantinescu and Nicole Casadevall and William 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… 

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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.

Identification of an Acquired JAK2 Mutation in Polycythemia Vera*

TLDR
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.

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TLDR
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.

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TLDR
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TLDR
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