Effect of Methylation Inhibitors on Phorbol Ester Induced Differentiation of HL-60 Promyelocytic Leukemia Cells

Cells of the promyelocytic leukemia line, HL-60, differentiate into a macrophage-like cell in response to phorbol-12-myristate-13-acetate (phorbol ester). The discrete changes include adherence to surfaces, motility and acquisition of macrophage-like characteristics, including synthesis of discrete proteins (1–3). Of particular interest has been the observation that the methylation inhibitor, 3-deazaadenosine, blocked the phorbol ester induction of the differentiation functions, adherence and motility (3). Specifically, 3-deazaadenosine arrested the induction of a specific differentiation protein but had no effect on the early or late phosphorylation events initiated by phorbol esters (3,4).