Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis

Blood. 2014 Oct 16;124(16):2507-13; quiz 2615. doi: 10.1182/blood-2014-05-579136. Epub 2014 Jul 18.

Abstract

Janus kinase 2 (JAK2) mutations define polycythemia vera (PV). Calreticulin (CALR) and myeloproliferative leukemia virus oncogene (MPL) mutations are specific to JAK2-unmutated essential thrombocythemia (ET) and primary myelofibrosis (PMF). We examined the effect of these mutations on long-term disease outcome. One thousand five hundred eighty-one patients from the Mayo Clinic (n = 826) and Italy (n = 755) were studied. Fifty-eight percent of Mayo patients were followed until death; median survivals were 19.8 years in ET (n = 292), 13.5 PV (n = 267; hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.4-2.2), and 5.9 PMF (n = 267; HR, 4.5; 95% CI, 3.5-5.7). The survival advantage of ET over PV was not affected by JAK2/CALR/MPL mutational status. Survival in ET was inferior to the age- and sex-matched US population (P < .001). In PMF (n = 428), but not in ET (n = 576), survival and blast transformation (BT) were significantly affected by mutational status; outcome was best in CALR-mutated and worst in triple-negative patients: median survival, 16 vs 2.3 years (HR, 5.1; 95% CI, 3.2-8.0) and BT, 6.5% vs 25% (HR, 7.6; 95% CI, 2.8-20.2), respectively. We conclude that life expectancy in morphologically defined ET is significantly reduced but remains superior to that of PV, regardless of mutational status. In PMF, JAK2/CALR/MPL mutational status is prognostically informative.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Calreticulin / genetics*
  • Cohort Studies
  • Female
  • Humans
  • Janus Kinase 2 / genetics*
  • Male
  • Middle Aged
  • Mutation*
  • Polycythemia Vera / diagnosis
  • Polycythemia Vera / genetics*
  • Primary Myelofibrosis / diagnosis
  • Primary Myelofibrosis / genetics*
  • Prognosis
  • Receptors, Thrombopoietin / genetics*
  • Survival Analysis
  • Thrombocythemia, Essential / diagnosis
  • Thrombocythemia, Essential / genetics*
  • Young Adult

Substances

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