Cloning of PRV-1, a novel member of the uPAR receptor superfamily, which is overexpressed in polycythemia rubra vera

Abstract

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.

Analysis of CD177 neutrophil expression in β-thalassemia patients

“…NB1 glycoprotein is a ligand for platelet endothelial cell adhesion molecule‐1 (PECAM‐1), and participates in neutrophil transmigration (6). CD177 gene is highly homologous to a gene overexpressed in neutrophils from patients with polycythemia rubra vera called PRV‐1 (7). While studying CD177 mRNA expression in polycythemia vera (PV) patients, Zoi et al., (8) extended their study to include individuals with β‐thalassemia.…”

The presence of a significant association between elevated PRV‐1 mRNA expression and low plasma erythropoietin concentration in essential thrombocythaemia

“…The cloning of a novel gene named polycythaemia rubra vera‐1 (PRV‐1) which codes for a cell surface receptor was recently described by Temerinac et al . (17). They found that mRNA from the PRV‐1 gene was overexpressed in granulocytes from patients with PV, and occasionally in patients with ET and idiopathic myelofibrosis.…”

Granulocyte gene polymorphisms and mutations: effects on immune response and neutrophil proliferation

“…Polycythemia vera is a chronic disorder of haematopoiesis that is associated with the increased production or red blood cells, platelets and neutrophils. Temerinac and colleagues compared genes expressed in neutrophils from patients with polycythemia rubra vera with genes expressed by neutrophils from healthy subjects [14]. They found that high copy numbers of mRNA from one gene were present in neutrophils from patients with polycythemia vera, but nearly absent from neutrophils from healthy subjects.…”

“…They found that high copy numbers of mRNA from one gene were present in neutrophils from patients with polycythemia vera, but nearly absent from neutrophils from healthy subjects. They called this gene PRV‐1 [14]. Independently, Kissel and colleagues sequenced the gene that encodes NB1 glycoprotein and found that the NB1 gene was highly homologueous to PRV‐1 [15].…”

“…CD177 is located on chromosome 19q13·2 [14–16] and belongs to the leucocyte antigen 6 ( Ly‐6 ) or snake toxin gene family. This gene family is characterized by conserved 70–100 amino acid domains containing 10 cysteine residues.…”