Insulin-Like Growth Factor Binding Protein-1 Is Elevated in Patients With Polycythemia Vera and Stimulates Erythroid Burst Formation In Vitro

摘要: Previously, we found that, in the myeloproliferative disorder polycythemia vera (PV), circulating erythroid progenitor cells were hypersensitive to insulin-like growth factor I (IGF-I), an effect shown occur through IGF-I receptor. Also, of PV patients, receptor was hyperphosphorylated on tyrosine residues under basal conditions, and its phosphorylation response exogenous strongly augmented. Thus, because appeared play a role pathogenesis PV, wished assess level circulation these patients. Normally, most is bound specific high-affinity IGF binding proteins that can regulate activity. We determined levels two key proteins, IGFBP-1 IGFBP-3. In separate experiments, plasma samples from total 23 patients age- sex-matched with 41 normal individuals compared by radioimmunoassay. The (37.80 +/- 4.33 microg/L) more than fourfold higher normals (9.34 1.34 or secondary erythrocytosis (9.47 1.96 microg/L), whereas concentrations IGFBP-3 similar those subjects. Because may be influenced insulin, measured insulin same samples. Our data showed elevation could not attributed low substantial increase concentration confirmed ligand blots performed (125)I-IGF-I. either inhibitory stimulatory action different conditions. reasoned if for erythropoiesis, elevated help explain increased sensitivity observed PV. If inhibitory, it might suggest compensatory mechanism which induce negative modulator action, this case IGFBP-1. To distinguish between hypotheses, titrated presence respect burst formation strikingly stimulatory. coupled ability stimulate provide attractive account consequent overproduction red blood characteristic