Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
|
| pubmed:dateCreated |
1998-5-21
|
| pubmed:abstractText |
The t(8;21)-encoded AML1-ETO chimeric product is believed to be causally involved in up to 15% of acute myelogenous leukemias through an as yet unknown mechanism. To directly investigate the role of AML1-ETO in leukemogenesis, we used gene targeting to create an AML1-ETO "knock-in" allele that mimics the t(8;21). Unexpectedly, embryos heterozygous for AML1-ETO (AML1-ETO/+) died around E13.5 from a complete absence of normal fetal liver-derived definitive hematopoiesis and lethal hemorrhages. This phenotype was similar to that seen following homozygous disruption of either AML1 or CBFbeta. However, in contrast to AML1- or CBFbeta-deficient embryos, fetal livers from AML1-ETO/+ embryos contained dysplastic multilineage hematopoietic progenitors that had an abnormally high self-renewal capacity in vitro. To further document the role of AML1-ETO in these growth abnormalities, we used retroviral transduction to express AML1-ETO in murine adult bone marrow-derived hematopoietic progenitors. AML1-ETO-expressing cells were again found to have an increased self-renewal capacity and could be readily established into immortalized cell lines in vitro. Taken together, these studies suggest that AML1-ETO not only neutralizes the normal biologic activity of AML1 but also directly induces aberrant hematopoietic cell proliferation.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Core Binding Factor Alpha 2 Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RUNX1T1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Runx1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
May
|
| pubmed:issn |
0006-4971
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
91
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
3134-43
|
| pubmed:dateRevised |
2007-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:9558367-Animals,
pubmed-meshheading:9558367-Bone Marrow Cells,
pubmed-meshheading:9558367-Core Binding Factor Alpha 2 Subunit,
pubmed-meshheading:9558367-DNA-Binding Proteins,
pubmed-meshheading:9558367-Gene Expression Regulation, Developmental,
pubmed-meshheading:9558367-Genes, Lethal,
pubmed-meshheading:9558367-Hematopoiesis,
pubmed-meshheading:9558367-Hematopoietic Stem Cells,
pubmed-meshheading:9558367-Heterozygote,
pubmed-meshheading:9558367-Leukemia, Myeloid, Acute,
pubmed-meshheading:9558367-Liver,
pubmed-meshheading:9558367-Mice,
pubmed-meshheading:9558367-Mice, Transgenic,
pubmed-meshheading:9558367-Neoplasm Proteins,
pubmed-meshheading:9558367-Proto-Oncogene Proteins,
pubmed-meshheading:9558367-Recombinant Fusion Proteins,
pubmed-meshheading:9558367-Transcription Factors,
pubmed-meshheading:9558367-Yolk Sac
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
Expression of a knocked-in AML1-ETO leukemia gene inhibits the establishment of normal definitive hematopoiesis and directly generates dysplastic hematopoietic progenitors.
|
| pubmed:affiliation |
Departments of Pathology and Laboratory Medicine, Tumor Cell Biology, and Genetics, St Jude Children's Research Hospital, Memphis, TN, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|