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

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Abstract
The HL-60 cell line, derived from a patient with acute promyelocytic leukemia, proliferates continuously in suspension culture and consists predominantly (> 90%) of promyelocytes. These cells can be induced to differentiate to morphologically and functionally mature granulocytes by incubation with a wide variety of compounds. 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 .mu.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. 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. In addition to their well-characterized involvement in epithelial cell differentiation, retinoids may also be involved in the differentiation of certain hematopoietic cells.