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filingDate 2000-08-31-04:00^^<http://www.w3.org/2001/XMLSchema#date>
grantDate 2004-02-24-04:00^^<http://www.w3.org/2001/XMLSchema#date>
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publicationDate 2004-02-24-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber US-6696549-B1
titleOfInvention Antibodies to the cytoplasmic domain of the thrombopoietin receptor
abstract Impaired TPO-mediated platelet protein tyrosine phosphorylation was consistently observed in patients with polycythemia vera (PV) as well as those with idiopathic myelofibrosis (IMF), in contrast to patients with essential thrombocytosis, chronic myelogenous leukemia, secondary erythrocytosis, iron deficiency anemia, hemochromatosis or normal volunteers. Moreover, the platelet TPO receptor, Mpl, was not detectable by immunoblotting with an antibody to the extracellular domain, by chemical crosslinking of TPO to the surface of platelets, or by flow cytometry using an antibody to the extracellular domain, in 34 of 34 PV patients and also in 13 of 14 IMF patients. 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 detectablility of Mpl by these methods can be used 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.
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