Terminal differentiation of the human promyelocytic leukemia cell line, HL-60, in the absence of cell proliferation

Cancer Res. 1982 Nov;42(11):4421-6.

Abstract

Induction of differentiation of the human promyelocytic leukemia cell line, HL-60, by dimethyl sulfoxide was analyzed for a requirement for cell replication. The ability of HL-60 cells to undergo terminal granulocytic differentiation as judged by nitroblue tetrazolium reduction, phagocytosis, and morphological criteria was not impaired by a total block in cellular proliferation. Retinoic acid, actinomycin D, and butyric acid also induced differentiation of HL-60 cells in the absence of cell growth. These results and the earlier demonstration that phorbol ester-induced macrophage differentiation of HL-60 occurred independently of DNA synthesis indicate that in these leukemic cells there is a dissociation of proliferation and maturation. The ability of retinoic acid to enhance differentiation of HL-60 cells was not altered in the presence of various growth-inhibiting concentrations of two clinically useful chemotherapeutic agents: hydroxyurea and 1-beta-D-arabinofuranosylcytosine. These results suggest that combination therapy in a program aimed at both inhibiting proliferation and inducing differentiation of leukemia cells could be beneficial.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Cytarabine / pharmacology
  • Dimethyl Sulfoxide / pharmacology
  • Humans
  • Hydroxyurea / pharmacology
  • Kinetics
  • Leukemia, Myeloid, Acute / physiopathology*

Substances

  • Cytarabine
  • Hydroxyurea
  • Dimethyl Sulfoxide