Recombinant human interferon sensitizes resistant myeloid leukemic cells to induction of terminal differentiation

Steven Grant, Kapil Bhalla, I. Bernard Weinstein, Sidney Pestka, Maria D. Mileno, Paul B. Fisher

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Recombinant human leukocyte interferon (IFN-αA) inhibits growth of the human promyelocytic leukemic cell line HL-60 without inducing these cells to differentiate terminally. When IFN-αA is combined with agents capable of inducing differentiation in HL-60 cells, such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA), cis or trans retinoic acid (RA) or dimethylsulfoxide (DMSO), growth suppression and induction of differentiation are dramatically increased. By growing HL-60 cells in increasing concentrations of TPA, RA, or DMSO, a series of sublines have been developed which are resistant to the usual growth inhibition and induction of differentiation seen when wild type HL-60 cells are exposed to these agents. Treatment of these resistant HL-60 cells with the combination of IFN-αA and the appropriate inducer results, however, in a synergistic suppression in cell growth and a concomitant induction of terminal differentiation. The ability of interferon to interact synergistically with agents which promote leukemic cell maturation may represent a novel means of reducing resistant leukemic cell populations.

Original languageEnglish (US)
Pages (from-to)379-388
Number of pages10
JournalBiochemical and Biophysical Research Communications
Volume130
Issue number1
DOIs
StatePublished - Jul 16 1985

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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