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JAK2 Mutations are present in all cases of polycythemia vera

Leukemia volume 22, page 1289 (2008)Cite this article

The JAK2V617F point mutation has been described in 65–97% of patients with polycythemia vera (PV).1 Previously, 17 phenotypical cases of PV from a large group of patients from three institutions were initially reported as JAK2V617F negative.2 These cases were reanalyzed in detail to determine the cause, if any, of the JAK2V617F negativity. Reasons for this initial negativity included inaccurate clinical diagnosis, relatively insensitive laboratory techniques, insufficient material for retesting, and possible treatment effect. It was predicted that when tested appropriately, JAK2 mutations would be found in all new cases of PV.2

To address the assay sensitivity issue, we studied a total of 105 PV cases diagnosed by Polycythemia Vera Study Group criteria using three different assays of distinct analytical sensitivity. We defined the sensitivity by mixing DNA from JAK2V617F-containing human erythroid leukemia cells (HEL) with that from normal peripheral blood mononuclear cells, so that 1% sensitivity would detect one part of HEL DNA in 100 parts of normal DNA. The first method used was pyrosequencing, which involves synthetic nucleotide extension by DNA polymerase. The method reliably detects JAK2V617F when the mutant allele is greater than 5%.1 The second method was a standard amplification refractory mutation system (ARMS) PCR assay , which detects the mutant allele when it occupies more than 1% of total DNA.3 The third method was a modified highly sensitive ARMS assay.4 The analytic sensitivity of the modified ARMS assay reaches 0.1% and has a false positive rate of less than 0.01% (we found 1 positive case in 300 individuals without myeloid disorders).5 Of 105 PV cases, the combination of all three assays detected the JAK2V617F allele in 104. In the remaining case, the JAK2 exon 12 deletion (E543–D544 del) was detected. Therefore, mutations in JAK2 have been detected in 100% of 105 PV patients examined.

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References

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Molecular Hematopathology Laboratory, Weill Medical College of Cornell University, New York, NY, USA

    Y L Wang

  2. Division of Hematology–Oncology, Department of Medicine, Weill Medical College of Cornell University, New York, NY, USA

    K Vandris, F Adriano & R T Silver

  3. Wessex Regional Genetics Laboratory, Salisbury District Hospital, University of Southampton, Salisbury, Wiltshire, UK

    A Jones & N C P Cross

  4. Division of Biostatistics and Epidemiology, Department of Public Health, Weill Medical College of Cornell University, New York, NY, USA

    P Christos

Authors
  1. Y L Wang
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  2. K Vandris
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  3. A Jones
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  4. N C P Cross
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  5. P Christos
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  6. F Adriano
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  7. R T Silver
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Correspondence to Y L Wang or R T Silver.

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Wang, Y., Vandris, K., Jones, A. et al. JAK2 Mutations are present in all cases of polycythemia vera. Leukemia 22, 1289 (2008). https://doi.org/10.1038/sj.leu.2405047

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