Faculty Collaboration Database

Effect of differentiation-inducing agents on oncogene expression in a chronic myelogenous leukemia cell line. Cancer 1988 Sep 15;62(6):1171-8

Date

09/15/1988

Pubmed ID

3044574

DOI

10.1002/1097-0142(19880915)62:6<1171::aid-cncr2820620621>3.0.co;2-8

Scopus ID

2-s2.0-0023772690 (requires institutional sign-in at Scopus site)   33 Citations

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, 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.

Author List

Eisbruch A, Blick M, Evinger-Hodges MJ, Beran M, Andersson B, Gutterman JU, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cell Differentiation
Cell Division
Cell Line
Fluorescent Antibody Technique
Hemin
Humans
Immunoenzyme Techniques
Leukemia, Myeloid
Models, Biological
Oncogenes
RNA, Neoplasm