Underlying mechanisms of the JAK2V617F mutation in the pathogenesis of myeloproliferative neoplasms

Pathologe. 2016 Nov;37(Suppl 2):175-179. doi: 10.1007/s00292-016-0240-2.

Abstract

Chronic myeloproliferative neoplasms (MPN) comprise a spectrum of clonal neoplastic disorders characterized by overproduction of terminally differentiated cells of the myeloid lineage. A common genetic basis for the BCR-ABL-negative MPN disorders was elucidated in 2005 with the identification of the JAK2V617F mutation in the majority of MPN patients. The discovery of JAK2V617F had a dramatic impact on the diagnosis and treatment of MPN. Testing for JAK2 mutations is now included in the World Health Organization (WHO) criteria for the diagnosis of MPN, and in 2011 the oral JAK2 kinase inhibitor ruxolitinib became the first Food and Drug Administration (FDA)-approved drug for the treatment of myelofibrosis. The drug is now also approved in Europe and Canada.

Keywords: Hematopoiesis; Myelofibrosis; Myeloproliferative neoplasms (MPN); Somatic mutation; Tyrosine kinase.

Publication types

  • Review

MeSH terms

  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / genetics*
  • DNA Mutational Analysis*
  • Hematologic Neoplasms / diagnosis
  • Hematologic Neoplasms / drug therapy
  • Hematologic Neoplasms / genetics*
  • Humans
  • Janus Kinase 2 / antagonists & inhibitors
  • Janus Kinase 2 / genetics*
  • Myeloproliferative Disorders / diagnosis
  • Myeloproliferative Disorders / drug therapy
  • Myeloproliferative Disorders / genetics*
  • Nitriles
  • Primary Myelofibrosis / drug therapy
  • Primary Myelofibrosis / genetics
  • Pyrazoles / therapeutic use
  • Pyrimidines

Substances

  • Nitriles
  • Pyrazoles
  • Pyrimidines
  • ruxolitinib
  • JAK2 protein, human
  • Janus Kinase 2