Retinoic acid combined with GM-CSF induces morphological changes with segmented nuclei in human myeloblastic leukemia...

The effects of all-trans retinoic acid (ATRA), either alone or in combination with GM-CSF, on the induction of differentiation of a human myeloblastic leukemia cell line, ML-1, were investigated. ATRA alone caused only slight induction of NBT-reducing activity even at a high concentration (10(-7) M), but when combined with GM-CSF, it led to remarkable increase in the induction of NBT-reducing activity. Synergistic effect of both agents was also observed on morphological changes and the inhibition of cell proliferation. When ATRA or GM-CSF was used alone, 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-synthesizing activity.