Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari syndrome

Gastroenterology. 2006 Jun;130(7):2031-8. doi: 10.1053/j.gastro.2006.04.008.

Abstract

Background & aims: Budd-Chiari Syndrome (BCS) results from obstruction to hepatic venous outflow, with myeloproliferative disorder (MPD) accounting for up to 40% of cases. A number of BCS cases labelled as "idiopathic" do not fulfill the diagnostic criteria for MPD but have features suggestive of a latent form based on hyperplastic bone marrow and erythroid progenitor cell culture; these cases may subsequently develop overt MPD. A clonal mutation in JAK2 tyrosine kinase (JAK2V617F) occurs in a high proportion of patients with MPD and is of use in the characterization of latent MPD in BCS.

Methods: We performed allele-specific polymerase chain reaction to screen for JAK2V617F in subjects with BCS (n = 41) and polycythemia vera (PV) (n = 20) and in hematologically normal controls (n = 27).

Results: AK2V617F was detected in 24 of 41 (58.5%) subjects with BCS, 19 of 20 PV controls, and 0 of 27 hematologically normal controls. Mean hemoglobin concentration and hematocrit were significantly higher in patients with JAK2V617F. Bone marrow was hyperplastic in 16 of 41 subjects (12/16 JAK2V617F positive). Nine of 33 (27.3%) showed endogenous erythroid colony formation (7/9 JAK2V617F positive). Eleven of 41 subjects developed overt MPD (8/11 essential thrombocythemia, 3/11 PV) after the diagnosis of BCS (median, 49 months; range, 8-87 months), and in 90.9% of these JAK2V617F was detected.

Conclusions: JAK2V617F occurs in a high proportion of patients with BCS. Latent MPD was missed in a substantial number of our subjects by using standard techniques. Such cases should be screened for JAK2V617F and carefully observed for the subsequent development of overt MPD.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Base Sequence
  • Budd-Chiari Syndrome / epidemiology
  • Budd-Chiari Syndrome / genetics*
  • Budd-Chiari Syndrome / physiopathology
  • Cohort Studies
  • Disease Progression
  • Female
  • Gene Expression Regulation
  • Genetic Markers
  • Humans
  • Janus Kinase 2
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation, Missense*
  • Polymerase Chain Reaction
  • Probability
  • Prognosis
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Retrospective Studies
  • Sensitivity and Specificity
  • Statistics, Nonparametric

Substances

  • Genetic Markers
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • JAK2 protein, human
  • Janus Kinase 2