RETINOIC ACID COMBINED WITH GM-CSF INDUCES MORPHOLOGICAL-CHANGES WITHSEGMENTED NUCLEI IN HUMAN MYELOBLASTIC-LEUKEMIA ML-1 CELLS

The effects of all-trans retinoic acid (ATRA), either alone or in comb ination with GM-CSF, on the induction of differentiation of a human my eloblastic leukemia cell line, ML-1, were investigated. ATRA alone cau sed only slight induction of NBT-1 reducing activity even at a high co ncentration (10(-7) M), but when combined with GM-CSF, it led to remar kable increase in the induction of NBT-reducing activity. Synergistic effect of both agents was also observed on morphological changes and t he inhibition of cell proliferation. When ATRA or GM-CSF was used alon e, neither parameter was changed substantially for long periods of up to 9 days. However, the combination of both agents induced remarkable morphological changes with segmented nuclei and also suppressed DNA-sy nthesizing activity.