TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis

Leukemia. 2009 May;23(5):905-11. doi: 10.1038/leu.2009.47. Epub 2009 Mar 5.

Abstract

High-throughput DNA sequence analysis was used to screen for TET2 mutations in bone marrow-derived DNA from 239 patients with BCR-ABL-negative myeloproliferative neoplasms (MPNs). Thirty-two mutations (19 frameshift, 10 nonsense, 3 missense; mostly involving exons 4 and 12) were identified for an overall mutational frequency of approximately 13%. Specific diagnoses included polycythemia vera (PV; n=89), essential thrombocythemia (ET; n=57), primary myelofibrosis (PMF; n=60), post-PV MF (n=14), post-ET MF (n=7) and blast phase PV/ET/MF (n=12); the corresponding mutational frequencies were approximately 16, 5, 17, 14, 14 and 17% (P=0.50). Mutant TET2 was detected in approximately 17 and approximately 7% of JAK2V617F-positive and -negative cases, respectively (P=0.04). However, this apparent clustering of the two mutations was accounted for by an independent association between mutant TET2 and advanced age; mutational frequency was approximately 23% in patients > or =60 years old versus approximately 4% in younger patients (P<0.0001). The presence of mutant TET2 did not affect survival, leukemic transformation or thrombosis in either PV or PMF; a correlation with hemoglobin <10 g per 100 ml in PMF was noted (P=0.05). We conclude that TET2 mutations occur in both JAK2V617F-positive and -negative MPN, are more prevalent in older patients, display similar frequencies across MPN subcategories and disease stages, and hold limited prognostic relevance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • DNA-Binding Proteins / genetics*
  • Female
  • Humans
  • Janus Kinase 2 / genetics
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Polycythemia Vera / genetics*
  • Primary Myelofibrosis / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Survival Rate
  • Thrombocythemia, Essential / genetics*

Substances

  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • TET2 protein, human
  • JAK2 protein, human
  • Janus Kinase 2