Novel somatic mutations of the VHL gene in an erythropoietin-producing renal carcinoma associated with secondary polycythemia and elevated circulating endothelial progenitor cells.
Therefore, in a patient with acquired erythrocytosis, it is reasonable to begin the diagnostic work-up with JAK2 mutation analysis to distinguish PV from secondary erythrocytosis.
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.
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.
However, until the recent description of the constitutively activating V617F point mutation of the Janus 2 tyrosine kinase (JAK2)--a high-frequency molecular marker that is extremely specific for clonal chronic myeloproliferative disorders--distinction of PV from secondary erythrocytosis or other conditions has often been difficult.
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.
Novel somatic mutations of the VHL gene in an erythropoietin-producing renal carcinoma associated with secondary polycythemia and elevated circulating endothelial progenitor cells.
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.
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.
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).
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.
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.
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.