The polycythaemia rubra vera‐1 gene is constitutively expressed by bone marrow cells and does not discriminate polycythaemia vera from reactive and other chronic myeloproliferative disorders

Abstract

Summary.Little is known about the expression of the polycythaemia rubra vera-1 (PRV-1) gene in bone marrow cells. To determine the expression level of PRV-1 in the bone marrow, we analysed PRV-1 quantitatively in Polycythaemia vera, other chronic myeloproliferative disorders, and reactive states. We demonstrated that PRV-1 was constitutively expressed in both myeloproliferative and reactive states. We concluded that, rather than an upregulation of the PRV-1 gene in the clonal haematopoiesis of polycythaemia vera, a failure to downregulate PRV-1 in granulocytes emigrating from the bone marrow might be responsible for the increase of transcripts in peripheral cells.

Chronic myeloproliferative disorders: molecular markers and pathogenesis

“…16 Surprisingly, analysis of PRV-1 did not reveal consistent differences in protein levels between PV and normal granulocytes. 17,18 Several studies confirmed a strong correlation (range of 70-100%) between the growth of EECs and increased granulocyte PRV-1 mRNA expression in PV, ET and IMF. 4,[19][20][21] Interestingly, increased expression of the transcriptional coactivator 'high mobility group protein A2' (HMGA2) was recently described as the first molecular marker for IMF.…”

JAK2V617F and the evolving paradigm of polycythemia vera

“…The development of reliable and clinically applicable assays for Epo has led to these assays being suggested as a more conclusive method to rule out secondary polycythemia [12, 13]. Alternative major or minor criteria for evidence of a myeloproliferative neoplasm include splenomegaly only apparent on radiologic studies [11], demonstration of erythroid colony formation in vitro without added Epo (endogenous erythroid colonies, or EEC) [14], increased expression of the platelet receptor Mpl [15], or of gene PRV-1 [16]. However, these alternatives, as expressed in the 2001 World Health Organization (WHO) criteria [17] (Table 2), preserved the basic structure and underlying assumptions of the PVSG criteria.…”

Stem Cell Defects in Philadelphia Chromosome Negative Chronic Myeloproliferative Disorders: A Phenotypic and Molecular Puzzle?

“…Several important investigations on aberrant processing and expression of growth factor receptors such as Mpl (Myeloproliferative leukaemia virus oncogene) and growth factors such as Transforming growth factor β-1 (TGFβ-1), growth factor hypersensitivity, endogenous erythroid colony (EEC) formation in PV, and introduction of diagnostic markers such as the Polycythaemia vera rubra receptor-1 (PRV-1) mRNA expression in granulocytes from peripheral blood but not bone marrow cells contributed substantially to expanding knowledge on the pathogenesis of Ph -CMPD [12][13][14][15][16][17][18][19]. In the process of myelofibrosis in Ph -CMPD, a series of studies demonstrated that apparently a cocktail of growth factors like TGFβ-1, basic fibroblast growth factor (bFGF) and platelet derived growth factor (PDGF) act in concert to induce and maintain fibrogenesis.…”