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Combinations of recombinant human interferons and retinoic acid
synergistically induce differentiation of the human promyelocytic leukemia
cell line HL-60
H Hemmi and TR Breitman
The human acute promyelocytic leukemia cell line HL-60 is induced to
differentiate into morphologically and functionally mature monocytelike
cells by incubation with a combination of 10 nmol/L retinoic acid (RA) and
various concentrations of recombinant immune interferon (rIFN- gamma).
These induced cells show marked increases in antibody-dependent cellular
cytotoxicity (ADCC), antibody-coated erythrocyte (EA) rosettes, nonspecific
esterase, and 5'-nucleotidase activity. rIFN- gamma alone at concentrations
of 10 to 1,000 U/mL has essentially no effect on morphological maturation,
nitroblue tetrazolium reduction, and immunophagocytosis. However,
rIFN-gamma at these concentrations increases EA rosetting in a
concentration-dependent manner that is not affected by 10 nmol/L RA. At a
concentration of 1,000 U/ml, rIFN-gamma induces moderate increases in
nonspecific esterase, 5'-nucleotidase, and ADCC. These parameters are
markedly increased by the addition of 10 nM RA, a concentration which alone
has no effect on these markers. Based on units of antiviral activity,
rIFN-gamma is tenfold more active than rIFN-alpha D in inducing EA rosettes
and 40-fold more active in inducing nitroblue tetrazolium reduction and
immunophagocytosis. These results, indicating that combinations of
rIFN-gamma or rIFN-alpha and RA synergistically induce differentiation of
HL-60, suggest that this combination may have clinical utility in the
treatment of patients with certain leukemias.
Volume 69,
Issue 2,
pp. 501-507,
02/01/1987
Copyright © 1987 by The American Society of Hematology
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