Induction of erythroid differentiation in leukemic K562 cells by an S-adenosylhomocysteine hydrolase inhibitor, aristeromycin

We have isolated an unusual nucleoside, aristeromycin, from the culture filtrate of Actinomycetes as a compound that induces normal morphology in v-abl^ts-NIH3T3 cells. Aristeromycin also induced erythroid differentiation in abl-expressing human chronic myelogenous leukaemia K562 cells. It did not affect the amount of Abl or the Abl-associated tyrosine kinase activity in either v-abl^ts-NIH3T3 or K562 cells. As a potent inhibitor of S-adenosylhomocysteine hydrolase, aristeromycin inhibited methylation of phosphatidylethanolamine to form phosphatidylcholine in K562 cells. Among aristeromycin analogues, the activity to inhibit S-adenosylhomocysteine hydrolase was paralleled with the induction of erythroid differentiation. Thus, aristeromycin inhibits abl functions indirectly, possibly by inhibiting biological methylations.