Standard Article

Somatic Mutations in Polycythaemia Vera and Other Philadelphia Chromosome Negative Myeloproliferative Neoplasms

  1. Lukasz P Gondek,
  2. Jerry L Spivak

Published Online: 17 DEC 2012

DOI: 10.1002/9780470015902.a0024249



How to Cite

Gondek, L. P. and Spivak, J. L. 2012. Somatic Mutations in Polycythaemia Vera and Other Philadelphia Chromosome Negative Myeloproliferative Neoplasms. eLS. .

Author Information

  1. Johns Hopkins University, Baltimore, Maryland, USA

Publication History

  1. Published Online: 17 DEC 2012


The just another kinase (JAK) family kinases function as the cognate tyrosine kinases for Type I/II cytokine receptors that lack intrinsic kinase domains. Perhaps the most important is JAK2, which is also a chaperone for the erythropoietin and thrombopoietin receptors as well as the kinase utilised alone or with other JAK kinases in the majority of cytokine receptors. JAK2 can be considered an oncogene because it is responsible for promoting cell proliferation and preventing apoptosis and its constitutive activation causes acute and chronic leukaemias and lymphomas. The most common JAK2-activating mutation, V617F, is responsible for the clinical phenotype of polycythaemia vera and that of approximately 50% of cases of essential thrombocytosis and primary myelofibrosis. In recent studies of JAK2 inhibitors in primary myelofibrosis there was amelioration of clinical symptoms and a reduction in splenomegaly, supporting an important role of JAK2 in the myeloproliferative phenotype and identifying a new treatment for these disorders.

Key Concepts:

  • The Janus kinase family has a crucial role in hematopoietic and immune cell function.

  • JAK2 V617F-activating mutation is the most frequent genetic alteration in polycythaemia vera, essential thrombocytosis and primary meylofibrosis.

  • JAK2 V617F has oncogenic properties and is responsible for uncontrolled cell proliferation, inhibition of apoptosis, genetic instability via induction of proto-oncogenes, reactive oxygen species and promotion of mitotic recombination.

  • JAK2 exon 12 mutations are frequent in JAK2 V617-negative polycythaemia vera patients.

  • JAK2 mutation alone cannot entirely explain the disease phenotype in the myeloproliferative disorders and genetic predisposition seems to play an important role in both the acquisition of these mutations and disease pathogenesis.

  • The role of JAK2 V617F mutation as a marker for disease prognosis is unresolved.

  • JAK2 inhibitors improve constitutional symptoms and reduce splenomegaly in primary myelofibrosis patients.


  • myeloproliferative neoplasms;
  • polycythaemia vera;
  • essential thrombocytosis;
  • primary myelofibrosis;
  • somatic mutations;
  • JAK2