Thrombotic risk correlates with mutational status in true essential thrombocythemia

Eur J Clin Invest. 2016 Aug;46(8):683-9. doi: 10.1111/eci.12647. Epub 2016 Jul 6.

Abstract

Background: True essential thrombocythemia (ET) may carry one of the known driver mutations (JAK2, MPL and CALR) or none of them [in triple-negative (3NEG) cases]. The patients' mutational status seems to delineate the clinical manifestations of ET.

Materials and methods: We report the data of 183 patients diagnosed with ET strictly according to the WHO 2008 criteria and with a full molecular diagnosis, including the following: 114 patients (62·3%) with JAK2V617F; 25 (13·7%) with CALR type 1 and 19 (10·4%) with CALR type 2; 3 (1·6%) with MPL; 22 (12%) who were 3NEG. Thrombotic risk was assessed by means of the IPSET-thrombosis score (IPSET-T).

Results: CALR and 3NEG patients had lower haemoglobin levels and leucocyte count than JAK2 patients. CALR patients, and those with type 2 in particular, had higher mean platelet counts and had extreme thrombocytosis more often than any of the other groups. Based on their IPSET-T stratification, 3NEG- and CALR-mutated patients belonged more frequently to the low-risk group and had a significant more favourable thrombosis-free survival rate than those with JAK2 mutation.

Conclusion: These findings indicate that the three different molecular markers have a significant impact on the clinical course of true ET, giving rise to different phenotypes of the same disease.

Keywords: CALR; JAK2V617F; MPL; essential thrombocythemia; myeloproliferative neoplasms.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Calreticulin / genetics
  • Female
  • Genetic Markers / genetics
  • Humans
  • Janus Kinase 2 / genetics
  • Leukocyte Count
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Phenotype
  • Platelet Count
  • Receptors, Thrombopoietin / genetics
  • Retrospective Studies
  • Risk Factors
  • Thrombocythemia, Essential / genetics*
  • Thrombosis / genetics*

Substances

  • Calreticulin
  • Genetic Markers
  • Receptors, Thrombopoietin
  • MPL protein, human
  • JAK2 protein, human
  • Janus Kinase 2