Daily addition of an anti-c-myc DNA oligomer induces granulocytic differentiation of human promyelocytic leukemia HL-60 cells in both serum-containing and serum-free media.

Abstract

Expression of the human protooncogene c-myc is necessary for replication, and may be inhibited in a sequence-specific, dose-dependent manner by an antisense oligodeoxynucleotide specific for the first five codons of c-myc mRNA. Antisense inhibition of c-myc inhibits the proliferation and enhances the differentiation of the HL-60 human promyelocytic leukemia cell line. In order to raise the efficacy of antisense oligomers, HL-60 cells were grown in a serum-free medium so as to minimize nuclease activity in the culture medium. Daily addition of anti-c-myc oligomer was then found to induce terminal granulocytic differentiation of 80% or more of HL-60 cells, and inhibit colony formation by greater than 50%, comparable to 1% Me2SO.