Source:http://linkedlifedata.com/resource/pubmed/id/12515728
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
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| pubmed:dateCreated |
2003-4-3
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| pubmed:abstractText |
The steps to leukemia following an in utero fusion of MLL (HRX, ALL-1) to a partner gene in humans are not known. Introduction of the Mll-AF9 fusion gene into embryonic stem cells results in leukemia in mice with cell-type specificity similar to humans. In this study we used myeloid colony assays, immunophenotyping, and transplantation to evaluate myelopoiesis in Mll-AF9 mice. Colony assays demonstrated that both prenatal and postnatal Mll-AF9 tissues have significantly increased numbers of CD11b(+)/CD117(+)/Gr-1(+/-) myeloid cells, often in compact clusters. The self-renewal capacity of prenatal myeloid progenitors was found to decrease following serial replating of colony-forming cells. In contrast, early postnatal myeloid progenitors increased following replating; however, the enhanced self-renewal of early postnatal myeloid progenitor cells was limited and did not result in long-term cell lines or leukemia in vivo. Unlimited replating, long-term CD11b/Gr-1(+) myeloid cell lines, and the ability to produce early leukemia in vivo in transplantation experiments, were found only in mice with overt leukemia. Prenatal Mll-AF9 tissues had reduced total (mature and progenitor) CD11b/Gr-1(+) cells compared with wild-type tissues. Colony replating, immunophenotyping, and cytochemistry suggest that any perturbation of cellular differentiation from the prenatal stage onward is partial and largely reversible. We describe a novel informative in vitro and in vivo model system that permits study of the stages in the pathogenesis of Mll fusion gene leukemia, beginning in prenatal myeloid cells, progressing to a second stage in the postnatal period and, finally, resulting in overt leukemia in adult animals.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
0006-4971
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
101
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
3229-35
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| pubmed:dateRevised |
2007-11-15
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| pubmed:meshHeading |
pubmed-meshheading:12515728-Age Factors,
pubmed-meshheading:12515728-Animals,
pubmed-meshheading:12515728-Bone Marrow,
pubmed-meshheading:12515728-Bone Marrow Transplantation,
pubmed-meshheading:12515728-Cell Aging,
pubmed-meshheading:12515728-Cell Transformation, Neoplastic,
pubmed-meshheading:12515728-Colony-Forming Units Assay,
pubmed-meshheading:12515728-Disease Progression,
pubmed-meshheading:12515728-Embryo, Mammalian,
pubmed-meshheading:12515728-Exons,
pubmed-meshheading:12515728-Female,
pubmed-meshheading:12515728-Gene Targeting,
pubmed-meshheading:12515728-Gestational Age,
pubmed-meshheading:12515728-Hematopoietic System,
pubmed-meshheading:12515728-Humans,
pubmed-meshheading:12515728-Immunophenotyping,
pubmed-meshheading:12515728-Leukemia, Experimental,
pubmed-meshheading:12515728-Liver,
pubmed-meshheading:12515728-Male,
pubmed-meshheading:12515728-Mice,
pubmed-meshheading:12515728-Models, Biological,
pubmed-meshheading:12515728-Mutagenesis, Insertional,
pubmed-meshheading:12515728-Myeloid Cells,
pubmed-meshheading:12515728-Myeloid-Lymphoid Leukemia Protein,
pubmed-meshheading:12515728-Oncogene Proteins, Fusion,
pubmed-meshheading:12515728-Organ Specificity,
pubmed-meshheading:12515728-Radiation Chimera,
pubmed-meshheading:12515728-Stem Cells
|
| pubmed:year |
2003
|
| pubmed:articleTitle |
Prenatal and postnatal myeloid cells demonstrate stepwise progression in the pathogenesis of MLL fusion gene leukemia.
|
| pubmed:affiliation |
University of Minnesota Cancer Center, Minneapolis, MN 55455, USA.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|