Linked Life Data

12393438

Source:http://linkedlifedata.com/resource/pubmed/id/12393438

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-1-16
pubmed:abstractText
The genetic defects underlying the pathogenesis of acute myeloid leukemia (AML) are still largely unknown. Retroviral insertion mutagenesis in mice has become a powerful tool to identify candidate genes involved in the development of leukemia and lymphoma. We have used this strategy with the 1.4 strain of Graffi murine leukemia virus (MuLV), which predominantly causes myeloid leukemias. Here, we report that Graffi-1.4-induced AML frequently harbors virus integrations in the gene encoding the transcription factor Yin Yang 1 (YY1). These integrations occurred in both orientations, and all were located in the 5' promoter region of the gene, 0.5 to 1.5 kb upstream of the major transcriptional start site. Luciferase reporter assays showed that virus integration in this region increases promoter activity and renders it independent of a functional binding site for Sp1, a major transcriptional regulator of YY1. We used the murine 32D model to study the consequence of perturbed YY1 expression for myelopoiesis. YY1 protein levels were high in 32D parental cells maintained in interleukin-3-containing medium, but they dropped when the cells were induced to differentiate by granulocyte-colony-stimulating factor (G-CSF). Strikingly, G-CSF-induced neutrophilic differentiation was reduced in 32D cell transfectants ectopically expressing YY1. In similar experiments on primary bone marrow cells, enforced YY1 expression blocked the outgrowth of CFU-GM colonies. Increased YY1 expression was seen in some cases of human AML. Collectively, these data imply a possible role of perturbed expression of YY1 in the development of AML through interference with the myeloid differentiation program in the leukemic progenitor cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1111-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12393438-Animals, pubmed-meshheading:12393438-Cell Differentiation, pubmed-meshheading:12393438-Cell Transformation, Neoplastic, pubmed-meshheading:12393438-Cell Transformation, Viral, pubmed-meshheading:12393438-DNA-Binding Proteins, pubmed-meshheading:12393438-Erythroid-Specific DNA-Binding Factors, pubmed-meshheading:12393438-Gene Expression Regulation, Leukemic, pubmed-meshheading:12393438-Granulocyte Colony-Stimulating Factor, pubmed-meshheading:12393438-Humans, pubmed-meshheading:12393438-Leukemia, Myeloid, pubmed-meshheading:12393438-Leukemia Virus, Murine, pubmed-meshheading:12393438-Mice, pubmed-meshheading:12393438-Myelopoiesis, pubmed-meshheading:12393438-Neutrophils, pubmed-meshheading:12393438-Oncogenes, pubmed-meshheading:12393438-Promoter Regions, Genetic, pubmed-meshheading:12393438-Transcription Factors, pubmed-meshheading:12393438-Virus Integration, pubmed-meshheading:12393438-YY1 Transcription Factor
pubmed:year
2003
pubmed:articleTitle
The gene encoding the transcriptional regulator Yin Yang 1 (YY1) is a myeloid transforming gene interfering with neutrophilic differentiation.
pubmed:affiliation
Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't