Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1988-10-3
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0008-543X
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
62
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1171-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Effect of differentiation-inducing agents on oncogene expression in a chronic myelogenous leukemia cell line.
pubmed:affiliation
Department of Oncology, Tel-Hashomer Hospital, Israel.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't