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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
1997-12-8
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pubmed:abstractText |
Thrombopoietin (TPO) is implicated as a primary regulator of megakaryopoiesis and thrombopoiesis through binding to the cytokine receptor c-Mpl (the product of the c-mpl proto-oncogene). In an effort to determine the pathophysiological role of TPO-c-Mpl system in essential thrombocythemia (ET), we have examined the levels of serum TPO and the expression and function of platelet c-Mpl in 17 patients with ET. In spite of extreme thrombocytosis, serum TPO levels were slightly elevated or within normal range in most, if not all, patients with ET (mean +/- SD, 1.31 +/- 1.64 fmol/mL), as compared with normal subjects (0.76 +/- 0.21 fmol/mL). Flow cytometric and Western blot analyses revealed that the expression of platelet c-Mpl was strikingly reduced in all patients with ET. Furthermore, the expression of platelet c-mpl mRNA was found to be significantly decreased in the ET patients tested. In contrast, almost identical levels of GPIIb/IIIa protein and mRNA were expressed in platelets from ET patients and normal controls. In addition to expression level, activation state of platelet c-Mpl was investigated in ET patients. Immunoblotting with anti-phosphotyrosine antibody showed that no aberrant protein-tyrosine phosphorylation was observed in platelets of ET patients before treatment with TPO, and the levels of TPO-induced protein-tyrosine phosphorylation, including c-Mpl-tyrosyl phosphorylation, roughly paralleled those of c-Mpl expression, suggesting that c-Mpl-mediated signaling pathway was not constitutively activated in platelets of ET patients. These results suggested that the TPO-c-Mpl system may not be directly linked to pathogenesis of ET, and that gene(s) mutated in ET may be important in regulating the levels of c-mpl gene expression in addition to the growth and differentiation of multipotential hematopoietic stem cells.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/MPL protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytokine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Thrombopoietin,
http://linkedlifedata.com/resource/pubmed/chemical/Thrombopoietin
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
|
pubmed:issn |
0006-4971
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pubmed:author |
pubmed-author:HashimotoKK,
pubmed-author:HorikawaYY,
pubmed-author:KanakuraYY,
pubmed-author:KatoTT,
pubmed-author:KosugiSS,
pubmed-author:KurataYY,
pubmed-author:MatsumuraII,
pubmed-author:MatsuzawaYY,
pubmed-author:MiyazakiHH,
pubmed-author:ShiragaMM,
pubmed-author:TadokoroSS,
pubmed-author:TomiyamaYY
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pubmed:issnType |
Print
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pubmed:day |
15
|
pubmed:volume |
90
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4031-8
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9354672-Adolescent,
pubmed-meshheading:9354672-Adult,
pubmed-meshheading:9354672-Aged,
pubmed-meshheading:9354672-Aged, 80 and over,
pubmed-meshheading:9354672-Blood Platelets,
pubmed-meshheading:9354672-Female,
pubmed-meshheading:9354672-Humans,
pubmed-meshheading:9354672-Male,
pubmed-meshheading:9354672-Middle Aged,
pubmed-meshheading:9354672-Neoplasm Proteins,
pubmed-meshheading:9354672-Proto-Oncogene Proteins,
pubmed-meshheading:9354672-RNA, Messenger,
pubmed-meshheading:9354672-Receptors, Cytokine,
pubmed-meshheading:9354672-Receptors, Immunologic,
pubmed-meshheading:9354672-Receptors, Thrombopoietin,
pubmed-meshheading:9354672-Thrombocytosis,
pubmed-meshheading:9354672-Thrombopoietin
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pubmed:year |
1997
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pubmed:articleTitle |
Markedly reduced expression of platelet c-mpl receptor in essential thrombocythemia.
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pubmed:affiliation |
Department of Internal Medicine II, Osaka University Medical School, Osaka, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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