Induction of differentiation of human and murine myeloid leukemia cells in culture by tunicamycin.

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Abstract
Tunicamycin, an antibiotic that specifically blocks the synthesis of N-acetylglucosamine-lipid intermediates and thereby prevents glycosylation of glycoproteins, induced differentiation of human (HL-60) and murine (Ml) myeloid leukemia cell lines in culture. At 0.1-1.0 .mu.g/ml, it induced differentiation of HL-60 and Ml cells, characterized by increase in phagocytic cells and changes to resemble mature myeloid cells. Fc receptors were induced in Ml but not in HL-60 cells; induction of intracellular lysozyme activity was not detected in HL-60 or Ml cells. With this concentration of tunicamycin, there was marked decrease in rate of incorporation of radioactive glucosamine into macromolecules and a decrease in the rate of DNA synthesis. Glycosylation of cellular proteins has an important role in maintaining these myeloid leukemia cells in an undifferentiated state in culture. Induction of phagocytosis in HL-60 and Ml myeloid leukemia cells and of Fc receptors in Ml cells does not require continued synthesis of the oligosaccharide portions of cellular proteins by the lipid-linked pathway.