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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
1988-10-3
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pubmed:abstractText |
K562 is a Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia (CML) blast crisis cell line representing a pluripotent precursor cell. At the molecular level, K562 cells express high levels of the aberrant bcr-abl product, p210bcr-abl, believed to be critical to the pathogenesis of CML. The authors demonstrate that exposure of K562 cells to hemin causes a state of partial, reversible erythroid maturation, accompanied by a marked decrease in p210bcr-abl. The change in bcr-abl expression may be mediated at the translational level since steady state amounts and enzymatic activity of the bcr-abl protein are reduced whereas bcr-abl mRNA levels are unaltered. The decrease in p210bcr-abl phosphokinase enzymatic activity can be detected within 2 hours after addition of hemin to the culture media, indicating that changes in expression of this oncogene probably occur before or concurrent with differentiation. No change in bcr-abl protein occurred in a CML cell line (KBM-5) which did not undergo differentiation after exposure to hemin, consistent with a direct relationship between altered p210bcr-abl expression and hemin-induced erythroid differentiation. Importantly, the marked diminution in bcr-abl protein was not associated with a disruption in K562 growth rates, indicating that the proliferative capacity of these cells may be independent of the bcr-abl product. In contrast to hemin, cytosine arabinoside (Ara-C) caused terminal erythroid differentiation of K562 cells, characterized by irreversible hemoglobin accumulation and cytostasis; and no change in bcr-abl protein expression was observed. The distinct effects of Ara-C and hemin could reflect the existence of pleiotropic differentiation pathways. Both Ara-C and hemin-exposed cells showed a decrease in c-myc and c-myb transcripts, suggesting that altered levels of these proto-oncogenes may be associated with erythroid maturation, regardless of the rate of cell division. K562 cells provide a useful model for analyzing the interaction between oncogene expression and CML cell growth and differentiation.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0008-543X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
62
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1171-8
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:3044574-Cell Differentiation,
pubmed-meshheading:3044574-Cell Division,
pubmed-meshheading:3044574-Cell Line,
pubmed-meshheading:3044574-Fluorescent Antibody Technique,
pubmed-meshheading:3044574-Hemin,
pubmed-meshheading:3044574-Humans,
pubmed-meshheading:3044574-Immunoenzyme Techniques,
pubmed-meshheading:3044574-Leukemia, Myeloid,
pubmed-meshheading:3044574-Models, Biological,
pubmed-meshheading:3044574-Oncogenes,
pubmed-meshheading:3044574-RNA, Neoplasm
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pubmed:year |
1988
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pubmed:articleTitle |
Effect of differentiation-inducing agents on oncogene expression in a chronic myelogenous leukemia cell line.
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pubmed:affiliation |
Department of Oncology, Tel-Hashomer Hospital, Israel.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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