INDUCTION OF DIFFERENTIATION AND DOWN-REGULATION OF C-MYB GENE-EXPRESSION IN ML-1 HUMAN MYELOBLASTIC-LEUKEMIA CELLS BY THE CLINICALLY EFFECTIVE ANTILEUKEMIA AGENT MEISOINDIGO

Meisoindigo, a second generation derivative of indirubin, is an effect ive chemotherapeutic agent with very low toxicity used in the treatmen t of chronic myeloid leukemia. To determine the nature of this activit y, the effect of a nontoxic concentration (0.72 mu g/mL) of this compo und on ML-1 human myeloblastic leukemic cells was examined. At such a concentration, differentiation induction was found to be the most pron ounced drug effect. During the 3-day drug incubation period, the viabl e cell number remained essentially constant, with approximately 48% of the cells demonstrating a mature phenotype with increased acid phosph atase activity and nitroblue tetrazolium dye reduction. As observed wi th other DNA-specific agents, induction of ML-1 differentiation by mei soindigo was accompanied by the down-regulation of c-myb gene expressi on. These data suggest that induction of leukemic cell differentiation associated with decreased c-myb expression may be one of the mechanis ms of the antitumor action of meisoindigo.