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The relationship of JAK2V617F and acquired UPD at chromosome 9p in polycythemia vera

Leukemia volume 28, pages 938–941 (2014)Cite this article

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JAK2V617F mutation is the most common somatic event observed in patients with myeloproliferative neoplasms (MPN).1, 2, 3, 4 JAK2V617F is found in over 95% of patients with polycythemia vera (PV), 55% of essential thrombocytosis and 65% of primary myelofibrosis (MF). Homozygous JAK2V617F is present in about half of PV patients, whereas it is rarely seen in other MPNs.3, 5, 6 Patients bearing homozygous JAK2V617F tend to have a longer duration of disease,2 higher hemoglobin levels, increased incidence of pruritis7 and are more likely to progress to post-PV MF.8 Homozygous JAK2V617F is shown to result from mitotic recombination, leading to acquired uniparental disomy (aUPD) on chromosome 9p.9

It was reported that JAK2 46/1 (GGCC) haplotype may predispose carriers to JAK2 mutation,10, 11, 12 and JAK2V617F facilitates the acquisition of homozygous JAK2.9, 13 Challenging this view was a single study reporting 9p aUPD in two PV subjects with wild-type JAK2,14 suggesting that in these two individuals, 9p aUPD might have preceded JAK2V617F. However, the relationship between JAK2V617F and 9p aUPD, the frequency and stability of existing PV genotypes has yet to be systematically defined in a larger PV cohort. To address this, we performed whole-exome sequencing and SNP array in 31 PV patients, and further validated our findings in two additional cohorts totaling 59 patients (Supplementary Methods). In addition, we investigated the stability of PV genotypes using 36 longitudinal samples.

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Acknowledgements

This study was supported by research funding from the National Human Genome Research Institute (NHGRI, Grant number: 5U54HG003273) to DW and from the National Institutes of Health (NIH, Grant number: NIH-P01CA108671) to JP. We thank MPD-RC consortium investigators and the MPD-RC Core laboratory for providing us with 109 additional PV samples for analysis. We thank Christian Buhay, Soo Kim, Charles White, Anton Ermeev, Donna Morton, Huyen Dinh, Ritika Raj, Lora Lewis, Christie Kovar, Sandra Lee, Michelle Bellair and Zhu Yiming for their excellent technical support.

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Author notes

  1. J T Prchal: JT Prchal also represents investigators of Myeloproliferative Disorders Research Consortium (MPD-RC).

Authors and Affiliations

  1. Human Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, TX, USA

    L Wang, K Walker, J Drummond, H Doddapaneni, J G Reid, D M Muzny, R A Gibbs & D A Wheeler

  2. Division of Hematology, The University of Utah School of Medicine Pathology/ARUP, and VAH, Salt Lake City, 84132, UT, USA

    S I Swierczek, L Lanikova, S J Kim, K Hickman & J T Prchal

  3. Zilkha Neurogenetic Institute and Norris Comprehensive Cancer Center, The University of Southern California, Los Angeles, 90089, CA, USA

    K Wang

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  1. L Wang
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Corresponding authors

Correspondence to D A Wheeler or J T Prchal.

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Supplementary Information accompanies this paper on the Leukemia website

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Wang, L., Swierczek, S., Lanikova, L. et al. The relationship of JAK2V617F and acquired UPD at chromosome 9p in polycythemia vera. Leukemia 28, 938–941 (2014). https://doi.org/10.1038/leu.2014.20

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