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Klinik für Innere Medizin IHämatologie, Onkologie und Stammzelltransplantation

Molecular heterogeneity in Essential Thrombycythemia

Essential Thrombocythemia (ET) is one of three diseases termed the chronic myeloproliferative disorders (MPDs). Besides ET this group includes Polycythemia vera (PV) and idiopathic myelofibrosis (IMF). The clinical presentation and course of patients with ET is very heterogeneous. The recent discovery of a point mutation in the JAK2 kinase (JAK2V617F) in only a proportion of ET patients (40 – 60 %) strengthens the hypothesis that several distinct alterations may lead to the development of this clinically defined disorder.Several molecular markers have been described in ET to date. Besides JAK2V617F, these include clonal hematopoiesis, endogenous erythroid colony (EEC) growth and PRV-1 overexpression. These markers allow the subclassification of ET patients and are potentially useful for the elucidation of distinct molecular disease etiologies. In addition, it has been proposed that hypersensitivity to thrombopoietin (TPO) underlies the development of ET and differentiates it from Polycythemia vera (PV), which is defined by IGF-1 hypersensitivity. However, the presence of molecular markers has not been correlated to growth factor hypersensitivity. Because of these advances, the following questions arise: 1) What alterations underlie the molecular etiology of JAK2wt/PRV-1 normal ET? 2) How does the identical mutation, JAK2V617F, lead to the wide variety of clinical presentations observed in MPD patients? 3) Can molecular markers be used for risk stratification in individual ET patients? Based on the following hypotheses, the Specific Aims of this project are therefore:

  1. Hypothesis: ET is comprised of at least two molecularily distinct entities, which give rise to a similar clinical phenotype. Aim: To perform microarray studies analyzing gene expression in 20 JAK2V617F/PRV-1 positive and 20 JAK2wt/PRV-1 negative ET patients.
  2. Hypothesis: Presence of JAK2V617F and PRV-1 overexpression are correlated with growth factor hypersensitivity. Aim: To determine TPO and IGF-1 hypersensitivities in a cohort of 15 JAK2V617F/PRV-1 positive and 15 JAK2wt/PRV-1 negative ET patients and to correlate the presence of JAK2V617F and PRV-1 overexpresion with this parameter.
  3. Hypothesis: PRV-1 mRNA overexpression leads to an increase in PRV-1 serum protein levels and this is correlated with the risk of developing thrombotic complications. Aim: To determine PRV-1 serum levels by ELISA in a cohort of 100 healthy controls and 140 ET patients and to assess whether PRV-1 protein levels correlate with thrombotic risk.


Current Lab Members on the Project

  • Dr. Wei Wang, Post doc (Ph. D. 2010)


  • Dr. Sven Schwemmers, Post doc (Ph. D. 2010)



  1. Wang W, Schwemmers S, Hexner EO, Pahl HL (2010) AML1 is overexpressed in patients with myeloproliferative neoplasms and mediates JAK2V617F-independent overexpression of NF-E2. Blood, 116: 254 - 266. (PDF-file)
  2. Schwemmers S, Will B, Waller CF, Abdulkarim K, Johansson P, Andreasson B, Pahl HL (2007) JAK2V617F-negative ET patients do not display constitutively active JAK/STAT signaling. Exp Hematol, 35 (11):1695 -1703. (PDF-file)
  3. Griesshammer M, Klippel S, Strunck E, Temerinac S, Mohr U, Heimpel H, Pahl HL (2004) PRV-1 mRNA expression discriminates two types of Essential Thrombocythemia., Ann. Hematol., 83: 364-370. (PDF-file)
  4. Goerttler PS, Steimle C, März E, Johansson PL, Andreasson B, Griesshammer M, Gisslinger H, Heimpel H, Pahl HL (2005) The Jak2V617F mutation, PRV-1 overexpression and EEC formation define a similar cohort of MPD patients. Blood, 106: 2862-2864. (PDF-file)
  5. Goerttler PS, März E, Johansson PL, Andreasson B, Kutti J, Moliterno AR, Marchioli R, Spivak JL, Pahl HL for the MPD Research Consortium (2005) Thrombotic and Bleeding Complications in Four Subpopulations of Patients with ET Defined by c-Mpl Protein Expression and PRV-1 mRNA Levels. Haematologica/The Hematology Journal, 90: 851-853. (PDF-file)

Principal Investigator

Prof. Dr. Heike L. Pahl

Chair: Section of Molecular Hematology
Department of Hematology / Oncology

Telefon +49 (0) 761 270-63400
Telefax +49 (0) 761 270-63410

Postal address:

Center for Tumor Biology
University Hospital Freiburg

Breisacher Str. 117
79106 Freiburg