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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2000-3-29
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pubmed:abstractText |
The thrombocytopenia and absent radii (TAR) syndrome is a rare disease associating bilateral radial agenesis and congenital thrombocytopenia. Here, we investigated in vitro megakaryocyte (MK) differentiation and expression of c-mpl in 6 patients. Using blood or marrow CD34(+) cells, the colony-forming unit (CFU)-MK number was markedly reduced. CD34(+) cells were also cultured in liquid medium in the presence of a combination of 3 cytokines (stem cell factor, interleukin-3, and interleukin-6) or megakaryocyte growth and development factor (PEG-rHuMGDF) with or without SCF. In the presence of PEG-rHuMGDF, the majority of mature megakaryocytes (CD41 high, CD42 high) underwent apoptosis. This phenomenon was also observed in cultures stimulated by three cytokines. However, this last combination of cytokines allowed a more complete terminal MK differentiation. Surprisingly, a homogeneous population of CD34(-)CD41(+)CD42(-) cells accumulated during the cultures. This population was unable to differentiate along the myeloid pathways. This result suggests that a fraction of MK cells is unable to differentiate in the TAR syndrome. We subsequently investigated whether this could be related to an abnormality in c-mpl. No mutation or rearrangement in the c-mpl gene was found by Southern blots or by sequencing of the c-mpl coding region and its promoter in any of the patients. Using Western blot analysis, a decreased level of Mpl was found in patient platelets. A decreased level of c-mpl messenger RNA in TAR platelets was also detected with a lower c-mpl-P to c-mpl-K ratio in comparison to adult platelets. Altogether, these results demonstrate that the thrombocytopenia of the TAR syndrome is associated with a dysmegakaryocytopoiesis characterized by cells blocked at an early stage of differentiation. (Blood. 2000;95:1633-1641)
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pubmed:language |
eng
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pubmed:journal |
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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, Thrombopoietin,
http://linkedlifedata.com/resource/pubmed/chemical/Thrombopoietin
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0006-4971
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pubmed:author |
pubmed-author:BoutardPP,
pubmed-author:DebiliNN,
pubmed-author:FavierRR,
pubmed-author:LazarVV,
pubmed-author:Le CouedicJ PJP,
pubmed-author:LetestuRR,
pubmed-author:MasséAA,
pubmed-author:PlasseMM,
pubmed-author:PlouvierEE,
pubmed-author:RameauPP,
pubmed-author:VainchenkerWW,
pubmed-author:VitratNN,
pubmed-author:VuillierJJ,
pubmed-author:WendlingFF
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
95
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1633-41
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:10688818-Adolescent,
pubmed-meshheading:10688818-Adult,
pubmed-meshheading:10688818-Bone Marrow,
pubmed-meshheading:10688818-Cell Differentiation,
pubmed-meshheading:10688818-Cell Lineage,
pubmed-meshheading:10688818-Cells, Cultured,
pubmed-meshheading:10688818-Child,
pubmed-meshheading:10688818-Child, Preschool,
pubmed-meshheading:10688818-Colony-Forming Units Assay,
pubmed-meshheading:10688818-DNA Mutational Analysis,
pubmed-meshheading:10688818-Female,
pubmed-meshheading:10688818-Fetal Diseases,
pubmed-meshheading:10688818-Gene Expression Regulation, Developmental,
pubmed-meshheading:10688818-Genes, Homeobox,
pubmed-meshheading:10688818-Hematopoiesis,
pubmed-meshheading:10688818-Hematopoietic Stem Cells,
pubmed-meshheading:10688818-Humans,
pubmed-meshheading:10688818-Male,
pubmed-meshheading:10688818-Megakaryocytes,
pubmed-meshheading:10688818-Middle Aged,
pubmed-meshheading:10688818-Neoplasm Proteins,
pubmed-meshheading:10688818-Proto-Oncogene Proteins,
pubmed-meshheading:10688818-RNA, Messenger,
pubmed-meshheading:10688818-Radius,
pubmed-meshheading:10688818-Receptors, Cytokine,
pubmed-meshheading:10688818-Receptors, Thrombopoietin,
pubmed-meshheading:10688818-Syndrome,
pubmed-meshheading:10688818-Thrombocytopenia,
pubmed-meshheading:10688818-Thrombopoietin
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pubmed:year |
2000
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pubmed:articleTitle |
Existence of a differentiation blockage at the stage of a megakaryocyte precursor in the thrombocytopenia and absent radii (TAR) syndrome.
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pubmed:affiliation |
INSERM U 362, Laboratoire associé no. 5 du comité de Paris de la Ligue Nationale, Institut Gustave Roussy, Villejuif, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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