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Clinical correlates of JAK2V617F allele burden in essential thrombocythemia
Article first published online: 17 APR 2007
Copyright © 2007 American Cancer Society
Volume 109, Issue 11, pages 2279–2284, 1 June 2007
How to Cite
Kittur, J., Knudson, R. A., Lasho, T. L., Finke, C. M., Gangat, N., Wolanskyj, A. P., Li, C.-Y., Wu, W., Ketterling, R. P., Pardanani, A. and Tefferi, A. (2007), Clinical correlates of JAK2V617F allele burden in essential thrombocythemia. Cancer, 109: 2279–2284. doi: 10.1002/cncr.22663
- Issue published online: 18 MAY 2007
- Article first published online: 17 APR 2007
- Manuscript Revised: 3 JAN 2007
- Manuscript Accepted: 3 JAN 2007
- Manuscript Received: 27 DEC 2006
- JAK2 V617F;
- essential thrombocythemia;
- allele burden
JAK2V617F occurs in approximately 50% of patients with essential thrombocythemia (ET). Qualitative studies of mutation analysis have previously reported an association between JAK2V617F and advanced age, higher hemoglobin level, higher leukocyte count, and lower platelet count. A possible association with thrombotic complication has also been considered.
Allele-specific, quantitative polymerase chain reaction (PCR) analysis for JAK2V617F was performed in 176 patients with ET using genomic DNA from archived bone marrow, which was collected within 1 year (n = 72 patients), between 1 and 5 years (n = 64 patients), or after 5 years (n = 40 patients) of diagnosis.
JAK2V617F was detected in 96 patients (55%), in whom mutant allele burden ranged from 1% to 100% (median, 6.3%). Neither mutational frequency (P = .37) nor mutant allele burden (P = .62) was affected by the timing of bone marrow sample collection. The presence of JAK2V617F was found to be significantly associated with higher hemoglobin level (P < .0001), lower platelet count (P = .001), higher leukocyte count (P = .008), increased incidence of venous thrombosis occurring after diagnosis (P = .02), and older age at diagnosis (P = .03). All but age retained significance in multivariable analysis. In mutation-positive patients (n = 96 patients), JAK2V617F allele burden clustered between 1% and 22% in 94 cases, in whom it correlated directly and significantly with platelet and leukocyte counts, palpable splenomegaly at diagnosis, and venous thrombosis occurring after diagnosis. The latter 2 associations remained significant with the inclusion of the remaining 2 outlier cases with 100% mutant allele burden; in addition, an association with male gender became evident.
JAK2V617F allele burden imparts additional phenotypic effects in ET. Cancer 2007. © 2007 American Cancer Society.