Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid

T R Breitman, S E Selonick, S J Collins, T R Breitman, S E Selonick, S J Collins

Abstract

The HL-60 cell line, derived from a patient with acute promyelocytic leukemia, proliferates continuously in suspension culture and consists predominantly (greater than 90%) of promyelocytes. These cells can be induced to differentiate to morphologically and functionally mature granulocytes by incubation with a wide variety of compounds, including butyrate and hypoxanthine and polar planar compounds such as dimethyl sulfoxide and hexamethylene bisacetamide. We have now found that retinoic acid (all-trans-retinoic acid) induces differentiation (as measured morphologically and by the ability to reduce nitroblue tetrazolium) of HL-60 at concentrations as low as 1 nM. Maximal differentiation (approximately 90%) occurs at 1 micro M, a concentration 1/500th to 1/160,000th the concentrations of butyrate (0.5 mM) and dimethyl sulfoxide (160 mM) that promote a similar increase in differentiation. Continuous exposure to retinoic acid is necessary for optimal differentiation, with the percentage of mature cells in the culture directly related to the length of time of exposure to retinoic acid. Retinoic acid and 13-cis-retinoic acid are equally effective in inducing differentiation of HL-60. Retinol (vitamin A), retinal, and retinyl acetate are approximately 1/1000th less potent. This study suggests that retinoids could provide a therapeutic tool in the treatment of acute myeloid leukemia, a disease that has been looked upon as primarily involving a block in myeloid differentiation, and indicates that retinoids, in addition to their well-characterized involvement in epithelial cell differentiation, may also be involved in the differentiation of certain hematopoietic cells.

References

    1. Proc Natl Acad Sci U S A. 1971 Feb;68(2):378-82
    1. Blood. 1975 Mar;45(3):321-34
    1. Eur J Cancer. 1974 Nov;10(11):731-7
    1. Int J Cancer. 1976 Mar 15;17(3):351-7
    1. Fed Proc. 1976 May 1;35(6):1332-8
    1. Blood. 1976 Aug;48(2):309-13
    1. Nature. 1976 Sep 9;263(5573):110-3
    1. Nature. 1977 Jun 16;267(5612):620-1
    1. J Natl Cancer Inst. 1977 Dec;59(6):1717-22
    1. Nature. 1977 Nov 24;270(5635):347-9
    1. Science. 1978 Jun 9;200(4346):1153-4
    1. Anal Biochem. 1978 Jun 1;86(2):743-50
    1. J Chromatogr. 1978 May 21;152(2):421-30
    1. Nature. 1978 Aug 3;274(5670):486-7
    1. Proc Natl Acad Sci U S A. 1978 May;75(5):2458-62
    1. Toxicol Appl Pharmacol. 1978 Apr;44(1):29-40
    1. Nature. 1978 Nov 16;276(5685):272-4
    1. Cell. 1978 Oct;15(2):393-403
    1. N Engl J Med. 1979 Feb 15;300(7):329-33
    1. Nature. 1979 Mar 8;278(5700):180-2
    1. Nature. 1979 Mar 22;278(5702):364-5
    1. Cancer Res. 1979 May;39(5):1661-6
    1. J Exp Med. 1979 Apr 1;149(4):969-74
    1. Blood. 1979 Sep;54(3):713-33
    1. Cancer Res. 1979 Oct;39(10):4055-7
    1. J Cell Biol. 1979 Aug;82(2):315-22
    1. Fed Proc. 1979 Oct;38(11):2510-4
    1. Fed Proc. 1979 Oct;38(11):2535-9
    1. Proc Natl Acad Sci U S A. 1980 Jan;77(1):457-61
    1. Int J Cancer. 1980 Feb 15;25(2):213-8

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