Serum Thrombopoietin and cMpl Expression in Thrombocytopenia of Different Etiologies
نویسندگان
چکیده
The relationship between thrombopoietin (TPO) and its receptor cMpl in thrombocytopenic conditions has not been entirely clarified. To elucidate this interplay may expand the spectrum of indications of TPO mimetics. In this study we have explored the relationship between TPO and cMpl in platelets and megakaryocytes of 43 patients with thrombocytopenia due to idiopathic thrombocytopenic purpura (ITP), bone marrow hypoplasia, myelodysplastic syndromes (MDS), and familial thrombocytopenia. Data were compared to cMpl and TPO in patients with a normal platelet count and in patients with thrombocytosis due to essential thrombocythemia (ET). All but familial patients showed higher TPO compared to controls. All thrombocytopenic states were invariably associated with increased expression of platelet cMPL compared to healthy controls. ET patients showed normal TPO and a trend toward a reduced cMpl expression. Immunofluorescence of bone marrow sections from patients with ITP and MDS failed to show a peculiar pattern compared to controls. Multiple mechanisms regulate TPO and cMpl in thrombocytopenic conditions.
منابع مشابه
Running title: c-Mpl P106L receptor processing and activation Category: Platelets and thrombopoiesis The thrombopoietin receptor P106L mutation functionally separates receptor signaling activity from thrombopoietin homeostasis
The interaction between thrombopoietin (THPO) and its receptor c-Mpl regulates downstream cytokine signaling and platelet homeostasis. Hereditary mutations of c-Mpl can either result in loss-of-function and thrombocytopenia or in gain-of-function and thrombocythemia and are important models to analyze the mechanism of c-Mpl activity. We have analyzed the effect of the c-Mpl P106L gain-of-functi...
متن کاملA rationally designed agonist antibody fragment that functionally mimics thrombopoietin.
By using rational design, antibody fragments (Fabs) that mimic thrombopoietin (TPO) were created. A peptide with cMpl receptor-binding capability was grafted into different complementarity-determining regions of a fully human Fab scaffold. Functional presentation of the peptide was optimized by using phage display and cell-based panning. Select antibodies and fragments containing two grafted pe...
متن کاملThrombopoietin: a potential diagnostic indicator of immune thrombocytopenia in pregnancy
To evaluate whether the serum thrombopoietin levels in pregnancy-associated immune thrombocytopenia (ITP) differ from those in gestational thrombocytopenia, and reveal the possibility of thrombopoietin serving as a marker for differential diagnosis. Serum thrombopoietin concentration was determined in ITP in pregnancy (n = 35), gestational thrombocytopenia (n = 31), healthy pregnancy (n = 32), ...
متن کاملOptimized Cytoplasmic Expression of Water Soluble Human Thrombopoietin in Modified Bacterial Strain
Background: Thrombopoietin is a glycoprotein produced by liver and kidney which is responsible for regulating the platelet production. Thrombopoietin is a key ligand with impact on regulating the self-renewal of Hematopoietic stem cells and the regulation of Megakaryocytes progenitors. Previous studies have indicated that only N-terminal domain of this protein has receptor promoting ability. Th...
متن کاملSerum thrombopoietin levels in cyclic thrombocytopenia.
Cyclic thrombocytopenia is a rare disorder characterized by periodic decreases and increases in platelet levels. Recent data suggest these fluctuations result from periodic failure of effective platelet production or periodic immune-mediated platelet destruction.’.’ However, the pathogenesis of this disorder is uncertain. We developed an enzyme-linked immunosorbent assay (ELISA) of serum thromb...
متن کامل