Mining for JAK-STAT mutations in cancer

Trends Biochem Sci. 2008 Mar;33(3):122-31. doi: 10.1016/j.tibs.2007.12.002.


The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway mediates signaling by cytokines, which control survival, proliferation and differentiation of several cell types. Constitutive JAK activation leads to persistent activation of STAT transcription factors, and several cancers exhibit constitutive STAT activation, in the absence of JAK or STAT activating mutations. Recently, a unique somatic mutation in JAK2 was identified in a majority of patients with myeloproliferative neoplasms. This mutation, encoding a V617F substitution, promotes JAK2 catalytic activation and cytokine-independent signaling. JAK2 and JAK3 mutations have also been identified in a minority of polycythemia vera and acute megakaryoblastic leukemia patients, and it is predicted that further JAK-STAT mutations will be identified in different cancers. Recent discoveries also suggest that mutated JAK proteins will be potent targets for anti-cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Janus Kinases / genetics
  • Janus Kinases / metabolism*
  • Models, Biological
  • Mutation*
  • Neoplasms / enzymology*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / metabolism*
  • Signal Transduction


  • STAT Transcription Factors
  • Janus Kinases