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Bone marrow JAK2V617F allele burden and clinical correlates in polycythemia vera

Leukemia volume 21, pages 2074–2075 (2007)Cite this article

More than 90% of patients with conventionally defined polycythemia vera (PV) are JAK2V617F-positive; the majority of the remaining carry other JAK2 exon 12 mutations.1 On the basis of PCR sequencing of granulocyte-derived DNA from PV patients, we have previously reported an association between homozygous, as opposed to heterozygous, JAK2V617F mutation pattern and a higher hemoglobin level and increased frequency of pruritus.2 These findings were recently confirmed by another study that used amplification-refractory mutation sequencing PCR assay3 to measure JAK2V617F allele burden from granulocyte-derived mRNA in 116 patients with PV (Vannucchi AM et al. Blood 2006; 108: Abstract no. 5); in addition, mutant allele burden in this particular study (median 38%) directly correlated with leukocyte count, spleen size, thrombosis risk and need for treatment. In the current Institutional Review Board-approved study, 103 consecutive patients with PV were selected based on availability of both clinical and laboratory information at diagnosis and archived bone marrow, collected either at the time of diagnosis or during the chronic phase of the disease. All patients fulfilled World Health Organization diagnostic criteria for PV.

Previously published methodology was used for measuring JAK2V617F allele burden in bone marrow-derived DNA.4 Quantitative PCR amplification and detection were performed on an ABI Prism 7900 HT Analyzer (Applied Biosystems, Foster City, CA, USA). Mutant allele burden was reported as the percentage of total JAK2 represented by JAK2V617F (that is JAK2V617F/JAK2V617F+JAK2 wild type).4 This JAK2V617F percentage was obtained from a standard curve for JAK2V617F/total JAK2 against ΔCt (CtJAK2V617F−CtJAK2WT), which was constructed using various proportions of genomic DNA from the cell lines K562 (homozygous for wild-type JAK2) and HEL (homozygous for JAK2V617F). Two microliters of each standard mixture (25 ng/μl) and each sample (25 ng/μl) were aliquoted into separate wells of the 96 well plate. Standards and samples were run in triplicate and the mean ΔCt, for each standard mixture and sample was used to plot the JAK2V617F/JAK2 total percentage.

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References

  1. Scott LM, Tong W, Levine RL, Scott MA, Beer PA, Stratton MR et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 2007; 356: 459–468.

    Article  CAS  Google Scholar 

  2. Tefferi A, Lasho TL, Schwager SM, Strand JS, Elliott M, Mesa R et al. The clinical phenotype of wild-type, heterozygous, and homozygous JAK2V617F in polycythemia vera. Cancer 2006; 106: 631–635.

    Article  CAS  Google Scholar 

  3. Vannucchi AM, Pancrazzi A, Bogani C, Antonioli E, Guglielmelli P . A quantitative assay for JAK2(V617F) mutation in myeloproliferative disorders by ARMS-PCR and capillary electrophoresis. Leukemia 2006; 20: 1055–1060.

    Article  CAS  Google Scholar 

  4. Levine RL, Belisle C, Wadleigh M, Zahrieh D, Lee S, Chagnon P et al. X-inactivation-based clonality analysis and quantitative JAK2V617F assessment reveal a strong association between clonality and JAK2V617F in PV but not ET/MMM, and identifies a subset of JAK2V617F-negative ET and MMM patients with clonal hematopoiesis. Blood 2006; 107: 4139–4141.

    Article  CAS  Google Scholar 

  5. Gale RE, Allen AJ, Nash MJ, Linch DC . Long-term serial analysis of X-chromosome inactivation patterns and JAK2 V617F mutant levels in patients with essential thrombocythemia show that minor mutant-positive clones can remain stable for many years. Blood 2007; 109: 1241–1243.

    Article  CAS  Google Scholar 

  6. Kittur J, Knudson RA, Lasho TL, Finke CM, Gangat N, Wolanskyj AP et al. Clinical Correlates of JAK2V617F Allele Burden in Essential Thrombocythemia. Cancer 2007; in press.

  7. Gangat N, Wolanskyj AP, McClure RF, Li CY, Schwager S, Wu W et al. Risk stratification for survival and leukemic transformation in essential thrombocythemia: a single institutional study of 605 patients. Leukemia 2007; 21: 270–276.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    A Tefferi, J J Strand, T L Lasho, C M Finke, N Gangat & A Pardanani

  2. Laboratorie of Cytogenetics, Mayo Clinic, Rochester, MN, USA

    R A Knudson & R P Ketterling

  3. Laboratorie of Hematopathology, Mayo Clinic, Rochester, MN, USA

    C A Hanson

Authors
  1. A Tefferi
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  2. J J Strand
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  3. T L Lasho
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  6. N Gangat
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  7. A Pardanani
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  8. C A Hanson
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  9. R P Ketterling
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Correspondence to A Tefferi.

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Tefferi, A., Strand, J., Lasho, T. et al. Bone marrow JAK2V617F allele burden and clinical correlates in polycythemia vera. Leukemia 21, 2074–2075 (2007). https://doi.org/10.1038/sj.leu.2404724

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