Progress in elucidation of molecular pathophysiology of myeloproliferative neoplasms and its application to therapeutic decisions

Int J Hematol. 2020 Feb;111(2):182-191. doi: 10.1007/s12185-019-02778-9. Epub 2019 Nov 18.


Myeloproliferative neoplasms (MPNs) are hematological diseases that are driven by somatic mutations in hematopoietic stem and progenitor cells. These mutations include JAK2, CALR and MPL mutations as the main disease drivers, mutations driving clonal expansion, and mutations that contribute to progression of chronic MPNs to myelodysplasia and acute leukemia. JAK-STAT pathway has played a central role in the disease pathogenesis of MPNs. Mutant JAK2, CALR or MPL constitutively activates JAK-STAT pathway independent of the cytokine regulation. Symptomatic management is the primary goal of MPN therapy in ET and low-risk PV patients. JAK2 inhibitors and interferon-α are the established therapies in MF and high-risk PV patients.

Keywords: Calreticulin; Hematological malignancy; Janus kinase; Myeloproliferative neoplasms; Thrombopoietin receptor.

Publication types

  • Review

MeSH terms

  • Calreticulin / genetics
  • Decision Making*
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Interferon-alpha / therapeutic use
  • Janus Kinase 2 / antagonists & inhibitors
  • Janus Kinase 2 / genetics
  • Mutation
  • Myeloproliferative Disorders / therapy*
  • Receptors, Thrombopoietin / genetics


  • CALR protein, human
  • Calreticulin
  • Enzyme Inhibitors
  • Interferon-alpha
  • Receptors, Thrombopoietin
  • MPL protein, human
  • JAK2 protein, human
  • Janus Kinase 2