Induction of differentiation of human monoblastic and myeloblastic leukemia cell lines by TNF muteins

The differentiation inducing activity of five recombinant human tumor necrosis factor (rHuTNF) muteins, prepared by protein engineering techniques, was compared by measuring the ability to reduce nitroblue tetrazolium dye of human myelogenous leukemia cells. TNF(C-Phe), in which the C-terminal leucine of TNF molecule was replaced by phenylalanine, was 20-times as potent in induction of differentiation of U-937 cells as the parent TNF(N-Met), in which methionine was added to N-terminal sequence of TNF. The differentiation inducing activity of TNF muteins was not always proportional to their binding activity to the receptors nor to their cytotoxicity on U-937 cells.