Premium
Effect of differentiation‐inducing agents on oncogene expression in a chronic myelogenous leukemia cell line
Author(s) -
Eisbruch Avraham,
Blick Mark,
EvingerHodges Mary Jeane,
Beran Miloslav,
Andersson Borje,
Gutterman Jordan U.,
Kurzrock Razelle
Publication year - 1988
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19880915)62:6<1171::aid-cncr2820620621>3.0.co;2-8
Subject(s) - chronic myelogenous leukemia , hemin , k562 cells , philadelphia chromosome , abl , cancer research , biology , leukemia , oncogene , cell culture , microbiology and biotechnology , cell , cell cycle , immunology , tyrosine kinase , signal transduction , biochemistry , enzyme , heme , genetics , chromosomal translocation , gene
Abstract 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, p210 bcr‐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 p210 bcr‐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 p210 bcr‐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 p210 bcr‐abl expression and hemin‐induced erythroid differentiation. Importantly, the marked diminuition 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.