BUTYRATE-INDUCED DIFFERENTIATION IN LEUKEMIC MYELOID CELLS - IN-VITROAND IN-VIVO STUDIES

A study of the effects of three differentiating agents, butyric acid, retinoic acid and cytosine arabinoside on proliferation and differenti ation of primary cultures, obtained from sixteen patients with myelo-p roliferative disorder was conducted. The results showed that BA was an effective inhibitor of cell proliferation and inducer of cytodifferen tiation. An acute non-lymphoblastic leukemia patient was treated with sodium butyrate. A temporary increase in differentiation-associated pa rameters were noted. However, the effects of SB were short-lived. The lack of clinical response led to the development of a BA prodrug pival oyloxymethylbutyrate (AN-9). This prodrug was more potent in vitro tha n BA in the induction of cytodifferentiation and inhibition of cell pr oliferation.