Factors affecting dysregulation of the JAK/STAT pathway

Dysregulated JAK/STAT signaling can arise from a number of abnormalities in the pathway, including excess cytokine activity and various mutations.6,7

 
 

The JAK2 V617F mutation is the most commonly observed mutation in MPNs. The V617F mutant JAK2 is constitutively activated and induces cytokine hypersensitivity, as well as growth factor–independent proliferation of hematopoietic stem cells.9-11 



 

Other important JAK pathway–activating mutations have also been documented in patients with MPNs, including those in MPL, and the recently discovered calreticulin (CALR) mutation, found to be present in most patients with primary myelofibrosis (PMF) and essential thrombocythemia (ET) who do not carry JAK2 or MPL mutations.8,12

 
 
 
 

References

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