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AssigneeThe Johns Hopkins University
InventorsJerry L Spivak, Alison Moliterno
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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.
A method of distinguishing polycythemia vera and idiopathic myelofibrosis from other diseases causing erythrocytosis, comprising the steps of:
A method of distinguishing polycytheia vera and idiopathic myelofibrosis from other diseases causing erythrocytosis, comprising the step of:
A method of distinguishing polycythemia vera and idiopathic myelofibrosis from other diseases causing erythrocytosis, comprising the steps of:
A method of distinguishing polycythemia vera and idiopathic myelofibrosis from other diseases causing erythrocytosis, comprising the steps of:
A method of distinguishing polycythemia vera (PV) and idiopathic myclofibrosis (IMF) from other diseases causing eiythrocytosis, comprising the step of:
A method of diagnosing polycythemia vera (PV) or idiopathic myelofibrosis (IMF) in an etythrocytotic patient, said method comprising determining the presence of an aberrant Mpl receptor in platelets or megakaryocytes of an erythrocytotic patient, and indicating that the patient has PV or IMF upon determining the presence of an aberrant Mpl receptor in the platelets or megakaryocytes.
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