The acquired single nucleotide valine to phenylalanine mutation (V617F) in the JAK2 tyrosine kinase is reported at variable frequencies in patients with the Philadelphia negative myeloproliferative disorders. As yet it is unclear whether its presence has an impact upon the clinical phenotype, complications or prognosis of these conditions. We have screened 87 patients under our care with myeloproliferative diseases (28 Polcythemia Vera [PV], 50 Essential Thrombocythemia [ET] and 9 Idiopathic Myelofibrosis[IMF]) using a modification of previously reported allele specific PCR on whole blood DNA (

Baxter,E.J et al
2005
Lancet
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365
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1054
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) and then correlated these results with clinical data. Overall there were 50 females and 37 males with a median age of 57.4 years (range 11–92) and median follow-up of 61.4 months (1–313). V617F was detected in 26 (93%) patients with PV, 26 (52%) ET and 2 (22%) IMF. Further analysis was performed to correlate V617F status with clinical features in the patients with ET. No survival data is presented for these patients due to the inherent bias in the analysis of fresh rather than archived samples. This will be performed in a prospective manner. However, one of the V617F positive ET patients subsequently died from AML, interestingly remaining heterozygous for this mutation. When comparing ET patients with detectable V617F against those without the mutation, the following significant differences were identified at the time of diagnosis: an older age (median 49.5 vs 39.3 years, p=0.04), higher haemoglobin (median 14 vs 13g/dl, p=0.03) and documented thrombotic events (11/26 vs 2/24, p=0.01). There were no significant differences in gender, platelet count at diagnosis or duration of follow-up. Overall thrombotic events were also more frequent in V617F positive patients (16/26 vs 7/24, p=0.02). There was no difference in thrombotic events following diagnosis (5/26 vs 5/24) or in the type of thromboses (microvasular, arterial or venous). Advanced age is a well established risk factor for thrombosis in ET, hence it is possible that V617F was associated with thrombosis as a consequence of the older age of our ET patients. Multivariate analysis was limited by small patient numbers and failed to demonstrate a significant predictive impact of either age or V617F mutation upon thrombosis. Ongoing studies will hopefully provide larger numbers for further analysis.

Topics:
hemoglobin, mutation, thrombocythemia, hemorrhagic, thrombosis, thrombus, follow-up, myeloproliferative disease, dna, myelofibrosis, idiopathic, chronic, nucleotides

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2005, The American Society of Hematology
2005
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