In K562 leukemia cells treated with doxorubicin and hemin, a decrease in c-myc mRNA expression correlates with loss of self-renewal capability but not with erythroid differentiation

Giuseppe Toffoli, Alessandra Viel, Carla Bevilacqua, Roberta Maestro, Loretta Tumiotto, Mauro Boiocchi

Research output: Contribution to journalArticle

Abstract

The decrease in c-myc mRNA expression occurring in leukemia cell lines induced to differentiate is supposed to be an early event of the commitment to the differentiation program. Alternatively, the decrease in c-myc mRNA expression could be simply a consequence of loss of the self-renewal capability characteristic of the terminal differentiated phenotypes. In an attempt to clarify these hypotheses, we analysed comparatively the kinetics of variations in c-myc mRNA expression, hemoglobin synthesis, DNA and RNA syntheses, cell cycle kinetics and self-renewal capability in normal and hemin-treated K562 leukemia cells exposed for different periods of time to the antitumoral antibiotic doxorubicin. Times of exposure to doxorubicin were either 2 h, which resulted in reversible induction of hemoglobin synthesis without significant cytostatic effects, or continuously for more than 5 days, which resulted in an irreversible induction of hemoglobin synthesis and in the complete and irreversible loss of self-renewal activity. Comparative analysis of the experimental data indicated that the decrease in c-myc mRNA expression correlated with the loss of replicative activity, possibly due to an irreversible cytostatic effect of the long exposure to doxorubicin, but not with the commitment to the differentiation programs.

Original languageEnglish
Pages (from-to)279-287
Number of pages9
JournalLeukemia Research
Volume13
Issue number4
DOIs
Publication statusPublished - 1989

Fingerprint

Hemin
K562 Cells
Doxorubicin
Leukemia
Messenger RNA
Hemoglobins
Cytostatic Agents
Cell Cycle
RNA
Anti-Bacterial Agents
Phenotype
Cell Line
DNA

Keywords

  • c-myc mRNA expression
  • cell growth kinetics
  • erythroid differentiation

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

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title = "In K562 leukemia cells treated with doxorubicin and hemin, a decrease in c-myc mRNA expression correlates with loss of self-renewal capability but not with erythroid differentiation",
abstract = "The decrease in c-myc mRNA expression occurring in leukemia cell lines induced to differentiate is supposed to be an early event of the commitment to the differentiation program. Alternatively, the decrease in c-myc mRNA expression could be simply a consequence of loss of the self-renewal capability characteristic of the terminal differentiated phenotypes. In an attempt to clarify these hypotheses, we analysed comparatively the kinetics of variations in c-myc mRNA expression, hemoglobin synthesis, DNA and RNA syntheses, cell cycle kinetics and self-renewal capability in normal and hemin-treated K562 leukemia cells exposed for different periods of time to the antitumoral antibiotic doxorubicin. Times of exposure to doxorubicin were either 2 h, which resulted in reversible induction of hemoglobin synthesis without significant cytostatic effects, or continuously for more than 5 days, which resulted in an irreversible induction of hemoglobin synthesis and in the complete and irreversible loss of self-renewal activity. Comparative analysis of the experimental data indicated that the decrease in c-myc mRNA expression correlated with the loss of replicative activity, possibly due to an irreversible cytostatic effect of the long exposure to doxorubicin, but not with the commitment to the differentiation programs.",
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AU - Toffoli, Giuseppe

AU - Viel, Alessandra

AU - Bevilacqua, Carla

AU - Maestro, Roberta

AU - Tumiotto, Loretta

AU - Boiocchi, Mauro

PY - 1989

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N2 - The decrease in c-myc mRNA expression occurring in leukemia cell lines induced to differentiate is supposed to be an early event of the commitment to the differentiation program. Alternatively, the decrease in c-myc mRNA expression could be simply a consequence of loss of the self-renewal capability characteristic of the terminal differentiated phenotypes. In an attempt to clarify these hypotheses, we analysed comparatively the kinetics of variations in c-myc mRNA expression, hemoglobin synthesis, DNA and RNA syntheses, cell cycle kinetics and self-renewal capability in normal and hemin-treated K562 leukemia cells exposed for different periods of time to the antitumoral antibiotic doxorubicin. Times of exposure to doxorubicin were either 2 h, which resulted in reversible induction of hemoglobin synthesis without significant cytostatic effects, or continuously for more than 5 days, which resulted in an irreversible induction of hemoglobin synthesis and in the complete and irreversible loss of self-renewal activity. Comparative analysis of the experimental data indicated that the decrease in c-myc mRNA expression correlated with the loss of replicative activity, possibly due to an irreversible cytostatic effect of the long exposure to doxorubicin, but not with the commitment to the differentiation programs.

AB - The decrease in c-myc mRNA expression occurring in leukemia cell lines induced to differentiate is supposed to be an early event of the commitment to the differentiation program. Alternatively, the decrease in c-myc mRNA expression could be simply a consequence of loss of the self-renewal capability characteristic of the terminal differentiated phenotypes. In an attempt to clarify these hypotheses, we analysed comparatively the kinetics of variations in c-myc mRNA expression, hemoglobin synthesis, DNA and RNA syntheses, cell cycle kinetics and self-renewal capability in normal and hemin-treated K562 leukemia cells exposed for different periods of time to the antitumoral antibiotic doxorubicin. Times of exposure to doxorubicin were either 2 h, which resulted in reversible induction of hemoglobin synthesis without significant cytostatic effects, or continuously for more than 5 days, which resulted in an irreversible induction of hemoglobin synthesis and in the complete and irreversible loss of self-renewal activity. Comparative analysis of the experimental data indicated that the decrease in c-myc mRNA expression correlated with the loss of replicative activity, possibly due to an irreversible cytostatic effect of the long exposure to doxorubicin, but not with the commitment to the differentiation programs.

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