title: Dkk3 levels in patients with myeloproliferative neoplasms.
abstract: BACKGROUND
  Dickkopf-3 (Dkk3) has been proposed as tumor suppressor gene and a marker for tumor blood vessels and has pro-angiogenic properties. Dkk3 is expressed in platelets and megakaryocytes from healthy controls and patients with BCR-ABL1-negative myeloproliferative neoplasms (MPN). The aim of this study is, to find out whether patients with MPN have higher Dkk3 serum levels than normal controls.
  
  
  METHODS
  We analyzed Dkk3 serum levels with ELISA in patients with newly diagnosed and untreated MPN, including 10 essential thrombocythemia (ET), 10 polycythemia vera (PV), 10 primary meylofibrosis (PMF) and 10 healthy blood donors and correlated these findings with biological and clinical key data and the JAK2-V617F status. Dkk3 levels were corrected to platelet count, Dkk3c, as patients with MPN have higher platelet counts than controls.
  
  
  RESULTS
  As expected, patients with MPN have higher platelet counts than normal controls. Dkk3 serum levels of patients with MPN (5.4 ± 6.1 ng/ml) showed no significant difference compared to normal controls (4.4 ± 3.8 ng/ml). Regarding Dkk3c, a significant difference to controls was found in PV (8.5 ± 8.7 ng/ml; p=0.04), but not in ET and PMF (5.7 ± 3.8 ng/ml; p=0.07 and 2.7 ± 3.6 ng/ml; p=0.9; respectively. Dkk3c correlated with the JAK2-V617F mutational burden (p=0.014, Rho=0.445).
  
  
  CONCLUSIONS
  Dkk3 levels corrected to platelet count showed higher levels in PV than normal controls. Elevated Dkk3c level could possibly correlate to platelet activation in PV patients and increased Dkk3 release. Whether this remains a surrogate marker of platelet release or it contributes to the thrombophilic state through its pro-angiogenic properties remains to be shown.
authors.affiliation: Department of Hematology, University Hospital Basel, Switzerland. Electronic address: medingerm@uhbs.ch.
authors.forename: Michael
authors.initials: M
authors.lastname: Medinger
authors.affiliation: Department of Hematology, University Hospital Basel, Switzerland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Muesser
authors.affiliation: Department of Hematology, University Hospital Basel, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Girsberger
authors.affiliation: Biomedicine, Experimental Hematology, University Hospital Basel, Switzerland.
authors.forename: Radek
authors.initials: R
authors.lastname: Skoda
authors.affiliation: Institute of Pathology, University Hospital Basel, Switzerland.
authors.forename: Alexandar
authors.initials: A
authors.lastname: Tzankov
authors.affiliation: Department of Hematology, University Hospital Basel, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Buser
authors.affiliation: Department of Hematology, University Hospital Basel, Switzerland.
authors.forename: Jakob
authors.initials: J
authors.lastname: Passweg
authors.affiliation: Department of Hematology, University Hospital Basel, Switzerland.
authors.forename: Dimitrios Α
authors.initials: DΑ
authors.lastname: Tsakiris
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018925:Chemokines; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000097:blood* / Q000235:genetics; D010976:Platelet Count; D017354:Point Mutation; D011087:Polycythemia Vera / Q000097:blood / Q000235:genetics; D055728:Primary Myelofibrosis / Q000097:blood / Q000235:genetics; D013920:Thrombocythemia, Essential / Q000097:blood / Q000235:genetics; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D053614:Janus Kinase 2
keywords: Dickkopf-3; Dkk3; ET; Essential Thrombocythemia; MPN; Myeloproliferative Neoplasms; Myeloproliferative neoplasm; PMF; PV; Platelets; Polycythemia Vera; Primary Meylofibrosis; Serum levels; TRAP-6; Thrombin Receptor-activating Peptide-6; VEGF; Vascular Endothelial Growth Factor