Phorbol ester induction of differentiation and apoptosis in the K562 cell line is accompanied by marked decreases in the stability of globin mRNAs and decreases in the steady state level of mRNAs encoding for ribosomal proteins L35, L31, L27, and L21.

To understand how phorbol ester induction switches the leukemia cell line K562 from erythroid specific gene expression to an apparently irreversible program of megakaryocytic gene expression, we used a subtractive cDNA cloning strategy to identify cDNA sequence tags whose expression was suppressed after exposure of K562 cells to phorbol ester. The switch from the erythroid to megakaryocytic phenotype of K562 cells is due, at least in part, to marked decreases in the half-lives of erythroid specific mRNAs. The phorbol ester induced decreases in the half-lives of erythroid specific mRNAs is reversed by cycloheximide or an inhibitor of protein kinase C. The phorbol ester induced shut off of cell division, and apparent terminal differentiation and apoptosis of K562 cells is also associated with a coordinate decrease in the expression of mRNAs that encode ribosomal proteins.