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Chronic Myeloproliferative Disorder

Prospective identification of high-risk polycythemia vera patients based on JAK2V617F allele burden

Leukemia volume 21, pages 1952–1959 (2007)Cite this article

Abstract

The aim of this study was to determine whether the burden of JAK2V617F allele correlated with major clinical outcomes in patients with polycythemia vera (PV). To this end, we determined JAK2 mutant allele levels in granulocytes of 173 PV patients at diagnosis. The mean (±s.d.) mutant allele burden was 52% (±29); 32 patients (18%) had greater than 75% mutant allele. The burden of JAK2V617F allele correlated with measurements of stimulated erythropoiesis (higher hematocrit, lower mean cell volume, serum ferritin and erythropoietin levels) and myelopoiesis (higher white cell count, neutrophil count and serum lactate dehydrogenase) and with markers of neutrophil activation (elevated leukocyte alkaline phosphatase and PRV-1 expression). As compared to those with less than 25% mutant allele, patients harboring greater than 75% JAK2V617F allele were at higher relative risk (RR) of presenting larger spleen (RR 4.7; P<0.001) or suffering from pruritus (RR 3.1; P<0.001). In these patients, the risk of requiring chemotherapy (RR 1.8; P=0.001) or developing major cardiovascular events (RR 7.1; P=0.003) during follow up were significantly increased. We conclude that a burden of JAK2V617F allele greater than 75% at diagnosis points to PV patients with high-risk disease.

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Acknowledgements

We are indebted to patients and their physicians for contributing to the study. Dr R Alterini and V Carrai helped in re-evaluation of bone marrow biopsies. We thank professor G Barosi for critically reviewing this paper. This study was supported in part by Associazione Italiana per la Ricerca sul Cancro, Milano; Ente Cassa di Risparmio di Firenze; Associazione Italiana per le Leucemie, Firenze; and Progetti del Ministero della Università e della Ricerca Scientifica (2006067001_003).

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Author notes

  1. A M Vannucchi, E Antonioli, P Guglielmelli, G Longo, A Pancrazzi, V Ponziani, C Bogani, P R Ferrini, A Rambaldi, V Guerini, A Bosi and T Barbui: The Myeloproliferative Disorders Research Consortium (MPD-RC), University of Illinois at Chicago, IL, USA.

Authors and Affiliations

  1. Department of Hematology, University of Florence, Florence, Italy

    A M Vannucchi, E Antonioli, P Guglielmelli, G Longo, A Pancrazzi, V Ponziani, C Bogani, P R Ferrini & A Bosi

  2. Division of Hematology, Ospedali Riuniti, Bergamo, Italy

    A Rambaldi, V Guerini & T Barbui

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  1. A M Vannucchi
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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Vannucchi, A., Antonioli, E., Guglielmelli, P. et al. Prospective identification of high-risk polycythemia vera patients based on JAK2V617F allele burden. Leukemia 21, 1952–1959 (2007). https://doi.org/10.1038/sj.leu.2404854

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