Consequences of the JAK2V617F allele burden for the prediction of transformation into myelofibrosis from polycythemia vera and essential thrombocythemia

Int J Hematol. 2015 Feb;101(2):148-53. doi: 10.1007/s12185-014-1721-9. Epub 2014 Dec 19.

Abstract

Patients diagnosed with polycythemia vera (PV) or essential thrombocythemia (ET) sometimes suffer transformation of the disease into myelofibrosis (MF), which is associated with a poorer prognosis. This study investigated the prognostic value of the allele burden of JAK2V617F, a somatic driver mutation in these diseases, by comparing the allele burden between formalin-fixed paraffin-embedded bone marrow collected at initial diagnosis and peripheral blood from follow-up visits. Although the annual changes in the JAK2V617F allele burden were comparable between MF-transformed (n = 11) and untransformed (n = 23) patients, the burden was significantly increased in MF-transformed patients exhibiting a longer disease duration than untransformed patients. Furthermore, MF transformation was only observed in patients whose JAK2V617F allele burden exceeded the mean values for each disease (PV, 71.7 %; ET, 35.5 %) at initial diagnosis or during follow-up. Finally, we showed that hydroxycarbamide treatment exerted neither a preventive effect on MF transformation nor a suppressive effect on the increased JAK2V617F allele burden. In conclusion, a high JAK2V617F allele burden at initial diagnosis or during follow-up is predictive of MF transformation in PV and ET. Therefore, routine measurement of the JAK2V617F allele burden using an accurate assay system is recommended to predict MF transformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Bone Marrow / pathology
  • Disease Progression
  • Humans
  • Hydroxyurea / therapeutic use
  • Janus Kinase 2 / genetics*
  • Mutation*
  • Polycythemia Vera / genetics*
  • Polycythemia Vera / pathology
  • Primary Myelofibrosis / diagnosis*
  • Primary Myelofibrosis / drug therapy
  • Primary Myelofibrosis / genetics*
  • Prognosis
  • Thrombocythemia, Essential / genetics*
  • Thrombocythemia, Essential / pathology
  • Time Factors

Substances

  • Janus Kinase 2
  • Hydroxyurea