Increased Dkk3 protein expression in platelets and megakaryocytes of patients with myeloproliferative neoplasms

Michael Medinger; Alexandar Tzankov; Johann Kern; Andreas Pircher; Martin Hermann; Helmut-Werner Ott; Günther Gastl; Gerold Untergasser; Eberhard Gunsilius

doi:10.1160/TH10-03-0172

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2011; 105(01): 72-80
DOI: 10.1160/TH10-03-0172

Platelets and Blood Cells

Schattauer GmbH

Increased Dkk3 protein expression in platelets and megakaryocytes of patients with myeloproliferative neoplasms

Michael Medinger

¹Tumor Biology & Angiogenesis Laboratory, Division of Hematology and Oncology, Innsbruck Medical University, Austria

,

Alexandar Tzankov

²Institute of Pathology, University Hospital Basel, Basel, Switzerland

,

Johann Kern

¹Tumor Biology & Angiogenesis Laboratory, Division of Hematology and Oncology, Innsbruck Medical University, Austria

,

Andreas Pircher

³Department of Internal Medicine V, Hematology and Oncology, Innsbruck Medical University, Innsbruck, Austria

,

Martin Hermann

⁴KMT Laboratory, Innsbruck Medical University, Innsbruck, Austria

,

Helmut-Werner Ott

⁵Institute of Medical and Chemical Laboratory Diagnostics (ZIMCL), University Hospital Innsbruck, Innsbruck, Austria

,

Günther Gastl

³Department of Internal Medicine V, Hematology and Oncology, Innsbruck Medical University, Innsbruck, Austria

,

Gerold Untergasser^*

¹Tumor Biology & Angiogenesis Laboratory, Division of Hematology and Oncology, Innsbruck Medical University, Austria

,

Eberhard Gunsilius^*

¹Tumor Biology & Angiogenesis Laboratory, Division of Hematology and Oncology, Innsbruck Medical University, Austria

› Institutsangaben

Abstract

Summary

Dickkopf-3 (Dkk3) has been proposed as tumour suppressor gene and a marker for tumour blood vessels. We analysed the expression and function of Dkk3 in platelets and megakaryocytes from healthy controls and patients with BCR-ABL1-negative myeloproliferative neoplasms (MPN). Dkk3 protein and gene expression in platelets was compared with endothelial and other blood cell populations by ELISA, real-time PCR, and immunofluorescence. Moreover, megakaryocytes were isolated from bone marrow aspirates by CD61 microbeads. Immunohisto-chemical studies of Dkk3 expression were performed in essential thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis (PMF) and control reactive bone marrow cases (each n=10). Compared to all other blood cell populations platelets showed the highest concentration of Dkk3 protein (150 ± 19 ng/mg total protein). A strong DKK3 gene and protein expression was also observed in isolated megakaryocytes. Dkk3 co-localised with VEGF in α-granules of platelets and was released similar to VEGF upon stimulation. Addition of recombinant Dkk3 had no influence on blood coagulation (aPTT, INR) and platelet aggregation. Significantly more Dkk3⁺ megakaryocytes/mm² could be found in bone marrow biopsies from patients with MPN (ET 40 ± 10, PV 31 ± 4, PMF 22 ± 3) than in controls (15 ± 3). The mean proportion of Dkk3⁺ megakaryocytes was increased in MPN as well (ET 83% ± 15%; PV 84% ± 12%; PMF 77% ± 8%) compared to controls (53% ± 11%). Dkk3⁺ megakaryocytes correlated with microvessel density in PV and PMF. We conclude that Dkk3 might be involved in the pathogenesis of MPN.

Keywords

Dickkopf-3 - platelets - megakaryocytes - myeloproliferative neoplasm

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Referenzen

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