Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-8-17
pubmed:abstractText
Some chromosomal translocations in acute leukemias involve the fusion of the trithorax-related protein Mll (also called HRX, All1, Htrx,) with a variety of heterologous proteins. In acute lymphoblastic leukemia associated with the t(4;11)(q21;q23) translocation, the 4q21 gene that fuses with Mll is AF4. To gain insight into the potential role of AF4 in leukemogenesis and development, this gene was inactivated by homologous recombination in mice. As expected from the tissue distribution of the AF4 transcript, development of both B and T cells is affected in AF4 mutant mice. A severe reduction of the thymic double positive CD4/CD8 (CD4(+)/CD8(+)) population was observed; in addition most double- and single-positive cells expressed lower levels of CD4 and CD8 coreceptors. Most importantly, the reconstitution of the double-positive compartment by expansion of the double-negative cell compartment was severely impaired in these mutant mice. In the bone marrow pre-B and mature B-cell numbers are reduced. These results demonstrate that the function of the mAF4 gene is critical for normal lymphocyte development. This raises the possibility that the disruption of the normal AF4 gene or its association with Mll function by translocation may orient the oncogenic process toward the lymphoid lineage. This represents the first functional study using a knock-out strategy on one of the Mll partner genes in translocation-associated leukemias. (Blood. 2000;96:705-710)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
96
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
705-10
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10887138-Animals, pubmed-meshheading:10887138-B-Lymphocytes, pubmed-meshheading:10887138-Bone Marrow Cells, pubmed-meshheading:10887138-CD4-Positive T-Lymphocytes, pubmed-meshheading:10887138-CD8-Positive T-Lymphocytes, pubmed-meshheading:10887138-DNA-Binding Proteins, pubmed-meshheading:10887138-Female, pubmed-meshheading:10887138-Glucocorticoids, pubmed-meshheading:10887138-Hematopoiesis, pubmed-meshheading:10887138-Lymphocyte Count, pubmed-meshheading:10887138-Lymphocytes, pubmed-meshheading:10887138-Male, pubmed-meshheading:10887138-Mice, pubmed-meshheading:10887138-Mice, Inbred BALB C, pubmed-meshheading:10887138-Mice, Knockout, pubmed-meshheading:10887138-Mutagenesis, pubmed-meshheading:10887138-Myeloid-Lymphoid Leukemia Protein, pubmed-meshheading:10887138-Nuclear Proteins, pubmed-meshheading:10887138-Proto-Oncogenes, pubmed-meshheading:10887138-T-Lymphocytes, pubmed-meshheading:10887138-Transcription Factors, pubmed-meshheading:10887138-Transfection, pubmed-meshheading:10887138-Translocation, Genetic
pubmed:year
2000
pubmed:articleTitle
Altered lymphoid development in mice deficient for the mAF4 proto-oncogene.
pubmed:affiliation
Centre d'immunologie INSERM-CNRS de Marseille Luminy, Marseille Cedex 9, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't