Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Molecular analysis of the human erythropoietin receptor (EpoR) promises to yield a greater mechanistic understanding of erythropoiesis and disease states that affect red cell production. The cloned receptor molecule is a 66 kDa membrane protein that is structurally related to a large superfamily of haemopoietin/growth factor receptors. The 66 kDa EpoR alone is capable of binding to erythropoietin (Epo) with nanomolar affinity. The native EpoR may form dimers before or after binding Epo. EpoR dimers and/or associated molecules are probably necessary for high-affinity Epo binding. The 66 kDa EpoR probably exists as a protein complex with as yet unidentified proteins of 100 and 85 kDa. The molecular mechanism of Epo signal transduction remains largely undefined. The possible role of the EpoR in human diseases has been studied in a variety of clinical conditions. A structurally abnormal EpoR gene has been identified in a human erythroleukemia cell line. In polycythemia vera, red cell progenitors exhibit exaggerated sensitivity to Epo and express only low-affinity EpoR. Some cases of hereditary polycythemia may be due to a mutant EpoR conferring enhanced Epo sensitivity. Other pathologic conditions may also be associated with abnormalities of the EpoR or its associated molecules. Soluble, immunoreactive EpoR is detectable in human serum, but its physiological significance is unknown.
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PMID:The human erythropoietin receptor. 145 11

Neutrophil granule subsets and dynamics were studied in 4 patients with polycythemia vera/myelofibrosis and 2 patients with chronic myelogenous leukemia. Alkaline phosphatase, a marker for the membrane of secretory vesicles (the most readily mobilizable pool of intracellular membranes in neutrophils) was highly elevated in the PV/MF patients and significantly reduced in the CML patients. In spite of this, the amount of secretory vesicles was normal as judged by the content of albumin, and of the membrane protein cytochrome b-245 and CD11b, both partially localized in secretory vesicles. Gelatinase granules were present in all patients. The azurophil granules were lighter than normal in both CML patients. SDS-PAGE protein profiles indicated absence of defensins from azurophil granules from 1 CML patient. In addition, a 41-42 kD doublet protein band was absent from 2 PV and 1 CML patient, and reduced in the other CML patient. No difference in mobilization of granules was observed between patient neutrophils and control neutrophils. Also, stimulation with 10(-8) mol/l N-formyl-methionyl-leucyl-phenylalanine induced normal increases in intracellular Ca2+ in patient neutrophils. These results indicate that stimulus-response coupling leading to granule exocytosis is intact in neutrophils from patients with myeloproliferative disorders.
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PMID:Mobilization of granules in neutrophils from patients with myeloproliferative disorders. 838 6

This study was aimed at the characterization of a gene expression signature of the pluripotent hematopoietic CD34(+) stem cell in idiopathic myelofibrosis (IM), which would eventually provide novel pathogenetic insights and/or diagnostic/prognostic information. Aberrantly regulated genes were revealed by transcriptome comparative microarray analysis of normal and IM CD34(+) cells; selected genes were also assayed in granulocytes. One-hundred seventy four differentially expressed genes were identified and in part validated by quantitative polymerase chain reaction. Altered gene expression was corroborated by the detection of abnormally high CD9 or CD164, and low CXCR4, membrane protein expression in IM CD34(+) cells. According to class prediction analysis, a set of eight genes (CD9, GAS2, DLK1, CDH1, WT1, NFE2, HMGA2, and CXCR4) properly recognized IM from normal CD34(+) cells. These genes were aberrantly regulated also in IM granulocytes that could be reliably differentiated from control polycythemia vera and essential thrombocythemia granulocytes in 100% and 81% of cases, respectively. Abnormal expression of HMGA2 and CXCR4 in IM granulocytes was dependent on the presence and the mutational status of JAK2(V617F) mutation. The expression levels of both CD9 and DLK1 were associated with the platelet count, whereas higher WT1 expression levels identified IM patients with more active disease, as revealed by elevated CD34(+) cell count and higher severity score. In conclusion, molecular profiling of IM CD34(+) cells uncovered a limited number of genes with altered expression that, beyond their putative role in disease pathogenesis, are associated with patients' clinical characteristics and may have potential prognostic application.
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PMID:Molecular profiling of CD34+ cells in idiopathic myelofibrosis identifies a set of disease-associated genes and reveals the clinical significance of Wilms' tumor gene 1 (WT1). 1699 May 84