Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari syndrome.
OBJECTIVE
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.
Patel
Raj K
RK
Department of Haematological Medicine, King's College Hospital, London, England. raj.patel@kingsch.nhs.uk
Lea
Nicholas C
NC
Heneghan
Michael A
MA
Westwood
Nigel B
NB
Milojkovic
Dragana
D
Thanigaikumar
Murugaiyan
M
Yallop
Deborah
D
Arya
Roopen
R
Pagliuca
Antonio
A
Gäken
Joop
J
Wendon
Julia
J
Heaton
Nigel D
ND
Mufti
Ghulam J
GJ
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D006502:Budd-Chiari Syndrome / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006801:Humans; D053614:Janus Kinase 2; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D011336:Probability; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
D005819:Genetic Markers; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2