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

Polycythemia vera (PV) is a clonal stem cell disorder characterized by hype rproliferation of the erythroid, myeloid, and megakaryocytic lineages. Alth ough it has been shown that progenitor cells of patients with PV are hypers ensitive to several growth factors, the molecular pathogenesis of this dise ase remains unknown. To investigate the molecular defects underlying PV, we used subtractive hybridization to isolate complementary DNAs (cDNAs) diffe rentially expressed in patients with PV versus normal controls. We isolated a novel gene, subsequently named PRV-1, which is highly expressed in granu locytes from patients with PV (n = 19), but not detectable in normal contro l granulocytes (n = 21), Moreover, PRV-1 is not expressed in mononuclear ce lls from patients with chronic myelogenous leukemia (n = 4) or acute myelog enous leukemia (n = 5) or in granulocytes from patients with essential thro mbocythemia (n = 4) or secondary erythrocytosis (n = 4), Northern blot anal ysis 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 granulocy tes from normal controls, stimulation of these cells with granulocyte colon y-stimulating factor induces PRV-1 expression. The PRV-1 cDNA encodes an op en 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 rep resents a novel hematopoietic receptor. (Blood.2000;95:2569-2576) (C) 2000 by The American Society of Hematology.