A NOVEL THROMBOPOIETIN SIGNALING DEFECT IN POLYCYTHEMIA VERA PLATELETS

摘要

Impaired TPO-mediated platelet protein tyrosine phosphorylation was consistently observed in patients with polycythemia vera (PV) as well as those with idiopathic myelofibrosis (IMF). The platelet TPO receptor, Mpl, was not detectable by immunoblotting with an antibody to the extracellular domain, by chemical cross-linking of TPO to the surface of platelets, or by flow cytometry using an antibody to the extracellular domain. Impaired TPO-induced protein tyrosine phosphorylation in PV and IMF platelets was uniformly associated with markedly reduced or absent expression of the extracellular domain of Mpl. Thus the reduced detectability of Mpl can be used as a marker of PV and IMF. The abnormality appears to distinguish PV from other forms of erythrocytosis and may be involved in the platelet function defect associated with PV.