Molecular aspects of myeloproliferative neoplasms

Int J Hematol. 2010 Mar;91(2):165-73. doi: 10.1007/s12185-010-0530-z. Epub 2010 Feb 27.


During these past 5 years several studies have provided major genetic insights into the pathogenesis of the so-called classical myeloproliferative neoplasms (MPNs): polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The discovery of the JAK2V617F mutation first, then of the JAK2 exon 12 and MPLW515 mutations, have modified the understanding of these diseases, their diagnosis, and management. Now it is established that almost 100% of PV patients present a JAK2 mutation. Nearly 60% of ET patients and 50% of patients with PMF have the JAK2V617F mutation. The MPLW515 mutations are also present in a small proportion of ET and PMF patients. These mutations are oncogenic events that cause these disorders; however, they do not explain the heterogeneity of the entities in which they occur. Genetic defects have not been yet identified in around 40% of ET and PMF. There are likely additional somatic genetic factors important for the MPN phenotype like the recently described TET2, ASXL1, and CBL mutations. Moreover, polymorphisms in the JAK2 gene have been recently described as associated with MPN. Additional studies of large cohorts are required to dissect the genetic events in MPNs and the mechanisms of these oncogenic cooperations.

Publication types

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

MeSH terms

  • DNA-Binding Proteins / genetics*
  • Dioxygenases
  • Humans
  • Janus Kinase 2 / genetics*
  • Myeloproliferative Disorders / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-cbl / genetics*
  • Receptors, Thrombopoietin / genetics*
  • Repressor Proteins / genetics*


  • ASXL1 protein, human
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Receptors, Thrombopoietin
  • Repressor Proteins
  • MPL protein, human
  • Dioxygenases
  • TET2 protein, human
  • Proto-Oncogene Proteins c-cbl
  • JAK2 protein, human
  • Janus Kinase 2
  • CBL protein, human