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Blood, Vol. 95 No. 8 (April 15), 2000:
pp. 2569-2576
Cloning of PRV-1, a novel member of the uPAR receptor superfamily,
which is overexpressed in polycythemia rubra vera
Sne ana Temerinac,
Steffen Klippel,
Elisabeth Strunck,
Sabine Röder,
Michael Lübbert,
Winand Lange,
Marc Azemar,
Gerold Meinhardt,
Hans-Eckart Schaefer, and
Heike
L. Pahl
From the Department of Experimental Anaesthesiology, University
Hospital Freiburg, Center for Tumor Biology, Freiburg, Germany; the
Department of Hematology and Oncology, University Hospital Freiburg,
Freiburg, Germany; the Center for Tumor Biology, Freiburg, Germany; the
Department of Hematology/Oncology, University Hospital Munich, Munich,
Germany; and the Department of Pathology, University Hospital Freiburg,
Freiburg, Germany.
Polycythemia vera (PV) is a clonal stem cell disorder characterized
by hyperproliferation of the erythroid, myeloid, and megakaryocytic lineages. Although it has been shown that progenitor cells of patients
with PV are hypersensitive to several growth factors, the molecular
pathogenesis of this disease remains unknown. To investigate the
molecular defects underlying PV, we used subtractive hybridization to
isolate complementary DNAs (cDNAs) differentially expressed in patients
with PV versus normal controls. We isolated a novel gene, subsequently
named PRV-1, which is highly expressed in granulocytes from patients
with PV (n = 19), but not detectable in normal control granulocytes
(n = 21). Moreover, PRV-1 is not expressed in mononuclear cells from
patients with chronic myelogenous leukemia (n = 4) or acute
myelogenous leukemia (n = 5) or in granulocytes from patients with
essential thrombocythemia (n = 4) or secondary erythrocytosis
(n = 4). Northern blot analysis showed that PRV-1 is highly expressed
in normal human bone marrow and to a much lesser degree in fetal liver.
It is not expressed in a variety of other tissues tested. Although
PRV-1 is not expressed in resting granulocytes from normal controls,
stimulation of these cells with granulocyte
colony-stimulating factor induces PRV-1 expression. The PRV-1 cDNA
encodes an open reading frame of 437 amino acids, which contains a
signal peptide at the N-terminus and a hydrophobic segment at the
C-terminus. In addition, PRV-1 contains 2 cysteine-rich domains
homologous to those found in the uPAR/Ly6/CD59/snake
toxin-receptor superfamily. We therefore propose that PRV-1
represents a novel hematopoietic receptor.
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