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MPL mutation effect on JAK2 46/1 haplotype frequency in JAK2V617F-negative myeloproliferative neoplasms

Leukemia volume 24, pages 859–860 (2010)Cite this article

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Consistent with an earlier suggestion of linkage disequilibrium between certain JAK2 haplotypes and polycythemia vera,1 three independent groups recently reported an association between a specific JAK2 haplotype, designated as 46/1, and JAK2V617F (VF)- or JAK2 exon 12 mutation-positive myeloproliferative neoplasms (MPNs).2, 3, 4, 5 We confirmed these observations in two recent papers6, 7 and also showed increased JAK2 46/1 haplotype frequency in VF-negative essential thrombocythemia (ET)6 and primary myelofibrosis (PMF).7 In the latter two studies, the JAK2 46/1 haplotype frequencies in both PMF (44%) and ET (41%) were significantly higher than that of the Wellcome Trust Case Control Consortium (WTCCC) (24%) or local (28%) control population, but similar in VF-positive versus VF-negative PMF (37 versus 36%) or ET (41 versus 38%), after adjusting for VF allele burden (that is, considering only patients with low allele burden to minimize allelic distortion from acquired uniparental disomy). A functional variant associated with the JAK2 46/1 haplotype could promote altered signaling and influence phenotype in the presence of VF or other JAK-STAT-relevant mutation, such as mutant MPL. Therefore, it is reasonable to consider the possibility that the increased JAK2 46/1 haplotype frequency seen in VF-negative MPN is attributed to the presence of a MPL mutation. The current study tests this hypothesis and also examines JAK2 46/1 haplotype frequency in MPL-mutated MPN.

Study patients were recruited from the Mayo Clinic database of adult PMF and ET patients, after obtaining permission from the institutional review board. Diagnosis was according to the World Health Organization criteria.8 JAK2V617F and MPL mutation analysis was performed using bone marrow-derived cells, using the previously published methods.9, 10 To screen for the JAK2 46/1 haplotype, we genotyped rs12343867 single nucleotide polymorphism (C/T; the C-allele tags the JAK2 46/1 haplotype),2 using a commercially available TaqMan SNP genotyping assay (Applied Biosystems Inc, Foster City, CA, USA). JAK2 46/1 haplotype allele frequencies in the study population were compared with those of population (WTCCC; n=1500) and local (n=57) controls.2

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Authors and Affiliations

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

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

  2. Cattedra ed U.O. di Ematologia, Policlinico Universitario di Palermo, Palermo, Italy

    D Caramazza & S Siragusa

  3. Division of Hematopathology, Department of Laboratory Medicine, Mayo Clinic, Rochester, MN, USA

    C A Hanson

Authors
  1. M M Patnaik
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  2. T L Lasho
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  3. C M Finke
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  9. A Tefferi
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Correspondence to A Tefferi.

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Patnaik, M., Lasho, T., Finke, C. et al. MPL mutation effect on JAK2 46/1 haplotype frequency in JAK2V617F-negative myeloproliferative neoplasms. Leukemia 24, 859–860 (2010). https://doi.org/10.1038/leu.2010.1

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