Source:http://linkedlifedata.com/resource/pubmed/id/14656889
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
|
| pubmed:dateCreated |
2004-3-22
|
| pubmed:abstractText |
The CCAAT/enhancer binding protein alpha (C/EBPalpha) is an essential transcription factor for granulocytic differentiation. C/EBPalpha mutations are found in approximately 8% of acute myeloid leukemia (AML) patients. Most of these mutations occur in the N-terminal coding region, resulting in a frame shift and the enhanced translation of a dominant-negative 30-kDa protein, which may be responsible for the differentiation block observed in AML. To test this hypothesis, we introduced a cDNA encoding an N-terminal mutated C/EBPalpha (mut10) into primary hematopoietic progenitors using a retroviral vector. Expression of mut10 in human CD34+ cord blood cells dramatically inhibited differentiation of both myeloid and erythroid lineages. Immunohistochemical analysis demonstrated coexpression of both myeloid and erythroid markers in the immature transformed cells. Surprisingly, mut10 did not block myelocytic differentiation in murine progenitors but did alter their differentiation kinetics and clonogenicity. Experiments were performed to confirm that the differential effect of mut10 on murine and human progenitors was not due to species-specific differences in C/EBPalpha protein sequences, expression levels, or inefficient targeting of relevant cells. Taken together, our results underline the intrinsic differences between hematopoietic controls in mouse and human and support the hypothesis that mutations in CEBPA are critical events in the disruption of myeloid differentiation in AMLs.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
0006-4971
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
103
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2744-52
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:14656889-Animals,
pubmed-meshheading:14656889-Bone Marrow Cells,
pubmed-meshheading:14656889-CCAAT-Enhancer-Binding Protein-alpha,
pubmed-meshheading:14656889-Cell Differentiation,
pubmed-meshheading:14656889-Cell Line,
pubmed-meshheading:14656889-Cells, Cultured,
pubmed-meshheading:14656889-Cloning, Molecular,
pubmed-meshheading:14656889-Erythroid Precursor Cells,
pubmed-meshheading:14656889-Female,
pubmed-meshheading:14656889-Fetal Blood,
pubmed-meshheading:14656889-Genes, Dominant,
pubmed-meshheading:14656889-Hematopoietic Stem Cells,
pubmed-meshheading:14656889-Humans,
pubmed-meshheading:14656889-Infant, Newborn,
pubmed-meshheading:14656889-Leukemia, Myeloid, Acute,
pubmed-meshheading:14656889-Mice,
pubmed-meshheading:14656889-Mice, Inbred C57BL,
pubmed-meshheading:14656889-Mutation,
pubmed-meshheading:14656889-Myeloid Progenitor Cells,
pubmed-meshheading:14656889-Recombinant Proteins,
pubmed-meshheading:14656889-Species Specificity
|
| pubmed:year |
2004
|
| pubmed:articleTitle |
A dominant-negative mutant of C/EBPalpha, associated with acute myeloid leukemias, inhibits differentiation of myeloid and erythroid progenitors of man but not mouse.
|
| pubmed:affiliation |
Molecular Pathology Group, Heinrich-Pette-Institut für Experimentelle Immunologie und Virologie, Hamburg, Germany.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|