Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2007-8-22
pubmed:abstractText
The 8;21 translocation is a common chromosomal abnormality in acute myeloid leukemia (AML). We recently identified a naturally occurring leukemogenic splice variant, AML1-ETO9a (acute myeloid leukemia-1 transcription factor and the eight-twenty-one corepressor-9a), of t(8;21). To understand the leukemic potential of AML1-ETO9a, we performed microarray analysis with the murine multipotential hematopoietic FDCP-mix A4 cell line. We identified changes in expression of various genes including CD44. CD44 is a type I transmembrane protein and functions as the major cellular adhesion molecule for hyaluronic acid, a component of the extracellular matrix. CD44 is expressed in most human cell types and is implicated in myeloid leukemia pathogenesis. We show that the presence of AML1-ETO9a significantly increased the expression of CD44 at both RNA and protein levels. Furthermore, the CD44 promoter is bound by AML1-ETO9a and AML1-ETO at the chromatin level. In addition, in the AML1-ETO9a leukemia mouse model CD44 is regulated in a cell context-dependent manner. Thus, our observations suggest that AML1-ETO and its splice variant AML1-ETO9a are able to regulate the expression of the CD44 gene, linking the 8;21 translocation to the regulation of a cell adhesion molecule that is involved in the growth and maintenance of the AML blast/stem cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0887-6924
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2010-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:17657222-Acute Disease, pubmed-meshheading:17657222-Alternative Splicing, pubmed-meshheading:17657222-Animals, pubmed-meshheading:17657222-Antigens, CD44, pubmed-meshheading:17657222-Cell Differentiation, pubmed-meshheading:17657222-Cell Division, pubmed-meshheading:17657222-Cell Survival, pubmed-meshheading:17657222-Chromosomes, Human, Pair 21, pubmed-meshheading:17657222-Chromosomes, Human, Pair 8, pubmed-meshheading:17657222-Core Binding Factor Alpha 2 Subunit, pubmed-meshheading:17657222-Gene Expression Regulation, Leukemic, pubmed-meshheading:17657222-Humans, pubmed-meshheading:17657222-K562 Cells, pubmed-meshheading:17657222-Leukemia, Myeloid, pubmed-meshheading:17657222-Mice, pubmed-meshheading:17657222-Neoplastic Stem Cells, pubmed-meshheading:17657222-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:17657222-Oncogene Proteins, Fusion, pubmed-meshheading:17657222-Translocation, Genetic
pubmed:year
2007
pubmed:articleTitle
The multi-functional cellular adhesion molecule CD44 is regulated by the 8;21 chromosomal translocation.
pubmed:affiliation
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural