New facts and speculations on human myeloid leukemias

The Hl-60 cell line, derived from a patient with acute promyelocytic leukemia, proliferates continuously in suspension culture and consists predominantly 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 dimethylsulfoxide and hexamethylene bisacetamide. However, these compounds are either nonphysiological or induce HL-60 at concentrations that are markedly greater than physiological. We have now found that retinoic acid is the most potent inducer of granulocytic differentiation of HL-60. This compound induces differentiation at concentrations 1/10(3) to 1/10(6) the concentration of other inducers and at concentrations that are physiological. These findings prompted an investigation of the sensitivity to retinoic acid of fresh human myelocytic leukemia cells in primary suspension culture. Of 21 leukemic specimens, only cells from the 2 patients with acute promyelocytic leukemia differentiated in response to retinoic acid. Thus, as with HL-60, it appears that retinoic acid specifically induces granulocytic differentiation of leukemic promyelocytes and may have therapeutic utility in the treatment of acute promyelocytic leukemia. In addition, our results suggest that retinoic acid may also be involved in the differentiation of certain hematopoietic cells.