Linked Life Data

17510218

Source:http://linkedlifedata.com/resource/pubmed/id/17510218

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2007-8-7
pubmed:abstractText
Overexpression of the human HOXB4 has been shown to induce the expansion and self-renewal of murine hematopoietic stem cells. In preparation for clinical studies, we wished to investigate the effects of HOXB4 on cells from other species, in particular preclinical large animals such as dogs and nonhuman primates. Thus, we transduced CD34(+) cells from nonhuman primates, dogs, and humans with a HOXB4-expressing gammaretroviral vector and a yellow fluorescent protein-expressing control vector. Compared with the control vector, HOXB4 overexpression resulted in a much larger increase in colony-forming cells in dog cells (28-fold) compared with human peripheral blood, human cord blood, and baboon cells (two-, four-, and fivefold, respectively). Furthermore, we found that HOXB4 overexpression resulted in immortalization with sustained growth (>12 months) of primitive hematopoietic cells from mice and dogs but not from monkeys and humans. This difference correlated with increased levels of retrovirally overexpressed HOXB4 in dog and mouse cells compared with human and nonhuman primate cells. The immortalized cells did not show any evidence of insertional mutagenesis or chromosomal abnormalities. Competitive congenic transplantation experiments showed that HOXB4-expanded mouse cells engrafted well after 1 or 3 months of expansion, and no leukemia was observed in mice. Our findings suggest that the growth promoting effects of HOXB4 are critically dependent on HOXB4 expression levels and that this can result in important species-specific differences in potency. Disclosure of potential conflicts of interest is found at the end of this article.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1066-5099
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2074-81
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:17510218-Animals, pubmed-meshheading:17510218-Antigens, CD34, pubmed-meshheading:17510218-Cell Line, Transformed, pubmed-meshheading:17510218-Cell Proliferation, pubmed-meshheading:17510218-Cells, Cultured, pubmed-meshheading:17510218-Clone Cells, pubmed-meshheading:17510218-Dogs, pubmed-meshheading:17510218-Gene Expression Regulation, pubmed-meshheading:17510218-Hematopoietic Stem Cell Transplantation, pubmed-meshheading:17510218-Hematopoietic Stem Cells, pubmed-meshheading:17510218-Homeodomain Proteins, pubmed-meshheading:17510218-Humans, pubmed-meshheading:17510218-Mice, pubmed-meshheading:17510218-Mice, Inbred C57BL, pubmed-meshheading:17510218-Primates, pubmed-meshheading:17510218-Species Specificity, pubmed-meshheading:17510218-Transcription Factors, pubmed-meshheading:17510218-Transfection, pubmed-meshheading:17510218-Transplantation, Homologous
pubmed:year
2007
pubmed:articleTitle
Effects of HOXB4 overexpression on ex vivo expansion and immortalization of hematopoietic cells from different species.
pubmed:affiliation
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural