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The rate of transformation from JAK2-mutated ET to PV is influenced by an accurate WHO-defined clinico-morphological diagnosis

Leukemia volume 29, pages 992–993 (2015)Cite this article

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The discovery of specific founder driving mutations (JAK2V617F, MPL and calreticulin (CALR)) in myeloproliferative neoplasms (MPN) prompted studies to elucidate their correlation with the respective clinicohematologic phenotype and clinical course.1, 2, 3 It was postulated that JAK2-mutated essential thrombocythemia (ET) resembles polycythemia vera (PV) for similarities of hematological presentation and incidence of clinical manifestations.4, 5, 6 Moreover, conflicting data have been published regarding the rate of evolution to overt PV. We report here results from a large database of ET and PV patients strictly defined according to the 2008 updated WHO classification for MPN7 discuss the reported rates of conversion from ET to PV highlighting the role played by bone marrow (BM) morphology and associated clinical findings as well.

In a clinicopathological database of patients who were diagnosed and treated for ET8 and PV9 in seven international centers of excellence for MPN, eligibility criteria for entry were strictly based on the WHO-defined criteria,7 regarding also the recently approved proposal for an update.10 A total of 690 ET patients were recruited of whom 422 (61%) showed the JAK2V617F mutation. PV patients (397 cases) revealed either the JAK2V617F or JAK2 exon12 mutation and included a fraction of 140 cases (35%) consistent with masked PV (mPV).9 Diagnosis of mPV was established by hemoglobin (HB) levels of <18.5 g/dl in males (range 16.0–18.4 g/dl) and <16.5 g/dl in females (range 15.0–16.4 g/dl) along with characteristic BM findings in accordance with WHO guidelines7, 10 and subnormal serum erythropoietin levels, as well as no evidence of subnormal ferritin values or iron deficiency.9 Cytoreductive therapy was applied in 57% of patients with ET according to the thrombotic risk; in both mPV and overt PV patients, phlebotomy, hydroxyurea (70%) and alpha interferon were used with the same frequency.

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Acknowledgements

AMV and TB were supported by a grant from Associazione Italiana per la Ricerca sul Cancro (Milano) ‘Special Program Molecular Clinical Oncology 5 × 1000’ to AGIMM (AIRC-Gruppo Italiano Malattie Mieloproliferative) (project #1005).

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Author notes

  1. T Barbui, J Thiele, A Carobbio, A M Vannucchi and A Tefferi: These authors contributed equally to this work.

Authors and Affiliations

  1. Research Foundation, Papa Giovanni XXIII Hospital Bergamo, Bergamo, Italy

    T Barbui & A Carobbio

  2. Institute of Pathology, University of Cologne, Cologne, Germany

    J Thiele

  3. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

    A M Vannucchi

  4. Hematology Division, Mayo Clinic, Rochester, MN, USA

    A Tefferi

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  1. T Barbui
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  2. J Thiele
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  3. A Carobbio
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  4. A M Vannucchi
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Correspondence to T Barbui.

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Barbui, T., Thiele, J., Carobbio, A. et al. The rate of transformation from JAK2-mutated ET to PV is influenced by an accurate WHO-defined clinico-morphological diagnosis. Leukemia 29, 992–993 (2015). https://doi.org/10.1038/leu.2014.328

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