This is the first report which provides direct molecular genetic evidence of association between a somatic IRP1 loss-of-function mutation and PHEO and secondary polycythemia.
Within the 91 patients with normal p50 values, 46 (51%) had secondary erythrocytosis, 13 (14%) polycythemia vera and 32 (35%) idiopathic erythrocytosis.
Within the 91 patients with normal p50 values, 46 (51%) had secondary erythrocytosis, 13 (14%) polycythemia vera and 32 (35%) idiopathic erythrocytosis.
The overexpression of PRV-1 seems to be a useful tool for discriminating ET and PV from ST and SE, thus offering an innovative diagnostic approach on the basis of the detection of positive diagnostic criteria instead of exclusion criteria.
Application of PRV-1 mRNA expression level and JAK2V617F mutation for the differentiating between polycytemia vera and secondary erythrocytosis and assessment of treatment by interferon or hydroxyurea.
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).
In this study selected CD34+ peripheral blood (PB) cells from PV patients, PB healthy donors and patients with secondary polycythemia (SP) were investigated and compared concerning frequency, morphology, antigen expression, transcription of differentiation markers and proliferation as well as apoptosis rate following short-term culture.
Within the 91 patients with normal p50 values, 46 (51%) had secondary erythrocytosis, 13 (14%) polycythemia vera and 32 (35%) idiopathic erythrocytosis.
No increase of exon 2 mRNA was evident in the T cells of patients with PV, or in the ECFCs and T cells from patients with secondary polycythemia. p27 also had elevated mRNA expression in PV ECFCs, but to a lesser degree.
Thus, we discovered a novel biological pathway of soluble biglycan inducing HIF-2α protein stabilization and Epo production presumably in an oxygen-independent manner, ultimately giving rise to secondary polycythemia.
Novel somatic mutations of the VHL gene in an erythropoietin-producing renal carcinoma associated with secondary polycythemia and elevated circulating endothelial progenitor cells.
In secondary erythrocytosis, the elevated red cell count is powered by factors outside the erythroid compartment, for instance by raised erythropoietin (EPO) synthesis based on congenital defects of the oxygen-sensing pathway.
Thus, we discovered a novel biological pathway of soluble biglycan inducing HIF-2α protein stabilization and Epo production presumably in an oxygen-independent manner, ultimately giving rise to secondary polycythemia.
Therefore, in a patient with acquired erythrocytosis, it is reasonable to begin the diagnostic work-up with peripheral blood JAK2 mutation analysis and serum Epo measurement to distinguish PV from secondary erythrocytosis.
A hypercoagulable state was found in nine patients: secondary polycythemia in five; protein C deficiency in one; protein S deficiency in one; and factor V Leiden mutations in two.
No increase of exon 2 mRNA was evident in the T cells of patients with PV, or in the ECFCs and T cells from patients with secondary polycythemia. p27 also had elevated mRNA expression in PV ECFCs, but to a lesser degree.
Within the 91 patients with normal p50 values, 46 (51%) had secondary erythrocytosis, 13 (14%) polycythemia vera and 32 (35%) idiopathic erythrocytosis.
X-chromosome DNA probes for the phosphoglycerate kinase (PGK) and hypoxanthine phosphoribosyl transferase (HPRT) genes were used to study clonality in haemopoietic cells from 63 women with myeloproliferative disease, idiopathic erythrocytosis, secondary erythrocytosis or normal red cell volumes.
No increase of exon 2 mRNA was evident in the T cells of patients with PV, or in the ECFCs and T cells from patients with secondary polycythemia. p27 also had elevated mRNA expression in PV ECFCs, but to a lesser degree.
Therefore, current diagnostic work-up for acquired polycythemia should start with peripheral blood JAK2 mutation screening, whereas VHL and/or EPOR mutations should be considered when CP is suspected.