Interferons induce normal and aberrant retinoic-acid receptors type α in acute promyelocytic leukemia cells: Potentiation of the induction of retinoid-dependent differentiation markers

Maurizio Gianní, Stefania Zanotta, Mineko Terao, Alessandro Rambaldi, Enrico Garattini

Research output: Contribution to journalArticle

Abstract

Treatment of the acute promyelocytic (APL) cell line NB4 with interferon α (IFNα), as well as IFNβ and γ, results in an increased expression of the transcripts coding for retinoic-acid receptor type alpha (RARα) and the leukemia-specific retinoic acid receptor PML-RAR. Transcriptional induction of the RARα and PML-RAR mRNAs is rapid and it is parallelled by an increase in the corresponding proteins. Up-regulation of RARα and PML-RAR gene expression by IFNα is accompanied by a strong potentiation in the induction of 2 retinoid-dependent granulocytic markers, i.e., granulocyte-colony-stimulating factor receptor mRNA and leukocyte alkaline phosphatase. However, IFNα does not have any effects on the retinoid-dependent regulation of the myeloid surface markers CD11b and CD33. The IFN-dependent increase in RARα levels and the enhancing effect of the cytokine an retinoid-dependent granulocytic markers expression may be a characteristic of PML-RAR positive cells, since the phenomena are not observed in HL-60 promyelocytes. Interferons as well as retinoids inhibit the growth of NB4 cells, although the 2 classes of compounds do not significantly interact in terms of anti-proliferative activity. These results suggest the possible use of combinations between IFNs and retinoic acid in the cyto-differentiating treatment of Apt. patients.

Original languageEnglish
Pages (from-to)75-83
Number of pages9
JournalInternational Journal of Cancer
Volume68
Issue number1
DOIs
Publication statusPublished - 1996

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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