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Klinik für Innere Medizin IHämatologie, Onkologie und Stammzelltransplantation

Molecular markers in Myeloproliferative Disorders

The gene for Polycythemia rubra vera-1 (PRV-1) was cloned in our laboratory by virtue of its overexpression in granulocytes from patients with Polcythemia vera (PV) compared to healthy controls (Temerinac, 2000). We and others have subsequently demonstrated that PRV-1 overexpression is specific for PV, since it does not occur in patients with secondary erythrocytosis (SE), secondary thrombocytosis (ST), CML or AML. Based on these data, we have developed a quantitative RT-PCR assay for the determination of PRV-1 mRNA levels, which can be used for the diagnosis of PV in patients with erythrocytosis (Klippel, 2003).However, in addition to PV patients, a subset of patients with Essential Thrombocythemia (ET), also overexpress PRV-1. In a cohort of 30 patients, we have demonstrated that PRV-1 overexpression correlates tightly with the ability to form EPO independent colonies (so called endogenous erythroid colonies, EECs) (Griesshammer, 2004).We subsequently determined whether PRV-1 positive and PRV-1 negative ET patients differ in their clinical course. In our cohort, PRV-1 positive ET patients had a statistically significantly higher incidence of thromboembolic or microcirculatory events (p=0.003) compared to PRV-1 negative patients. In addition, 40% of the PRV-1-positive patients develop signs and symptoms of PV during the course of their disease. In contrast, none of the 15 PRV-1-negative patients displayed such symptoms (p=0.017) (Griesshammer, 2004).PRV-1 is one of five molecular markers described in MPD patients, the others being a point mutation in the JAK2 kinase (JAK2V617F), the presence of EECs, clonal hematopoesis, the reduced expression of c-Mpl. Each of the markers is present in around 50% of ET patients. We therefore investigated whether these markers are acquired concurrently or separately in individual patients. Our results demonstrate that three of the markers, JAK2V617F, EEC formation, PRV-1 overexpression and clonality coincide in most patients, whereas reduced c-Mpl expression is acquired independently (Goerttler, 2005a and 2005b).On the basis of these data, we have postulated the distinction of two subtypes of ET: one that is characterized by the JAK2V617F mutation, the presence of EECs as well as PRV-1 overepression and the second, in which patients present with wt JAK2, absence of EECs and normal PRV-1 levels. Patients in the former category appear by retrospective analysis to be at higher risk for thromboembolic complications any may therefore profit from more aggressive therapy (Griesshammer 2004).

Current Lab Members on Project:

  • Jakob Meyer, M.D. student


  • Dr. med. Snezana Temerinac
  • Dr. Sven Schwemmers, Post doc (Ph. D. 2010)
  • Dr. Steffen Klippel (Ph. D. 2003)
  • Dr. Philipp Goerttler(Ph. D. 2005)
  • Dr. Cordula Steimle (Ph. D. 2005)


  1. Klippel S, Strunck E , Busse CE, Behringer D, Pahl HL (2002) Biochemical Characterization of PRV-1, a Novel Hematopoietic Cell Surface Receptor, which is Overexpressed in Polycythemia rubra vera., Blood, 100: 2441-2448
  2. Temerinac S, Klippel S, Strunck E, Röder S, Lübbert M, Lange W, Azemar M, Meinhardt G, Schaefer HE, Pahl HL (2000) Cloning of PRV-1, a Novel Member of the uPAR Receptor Superfamily, which is Overexpressed in Polycythemia rubra vera. Blood 95:2569
  3. Klippel S, Strunck E, Temerinac S, Meinhardt G, Mohr U, Leichtle R, Griesshammer M, Heimpel H, Pahl HL (2003) Quantification of PRV-1 mRNA distinguishes Polycythemia vera from Secondary Erythrocytosis., Blood, 102: 3569-3574.
  4. 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.
  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.
  6. 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.

Principal Investigator

Prof. Dr. Heike L. Pahl

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