Direct effects of 13-cis and all-trans retinoic acid on normal bone marrow (BM) progenitors : comparative study of BM mononuclear cells and on isolated CD34+ BM cells

The effects of both 13-cis-and all-trans retinoic acid (RA) on colony formation of normal bone marrow (BM) progenitors were investigated in semi-solid (methylcellulose) assays, using either isolated CD34+ cells or BM mononuclear cells. Single cell liquid cultures were performed to further discriminate between direct and indirect effects. RA action results in significant decrease of colony forming units (CFUs). This effect is more pronounced starting from CD34+ progenitors than starting from total BM. This overall decrease in CFUs is due to selective inhibition of CFU-M (macrophage) and erythroid colonies (BFU-E). At the single cell level the CFU-M inhibition is confirmed with--in addition--a significant inhibition of CFU-GM (granulocyte-macrophage) and a marked stimulation of CFU-G (granulocyte)s. Both retinoids exert the above-mentioned effects. All-trans RA, however, is effective at a tenfold lower concentration (10(-7)M) than 13-cis RA (10(-6)M). Results on CD34+ BM fractions (substantially reduced in accessory cells) demonstrate that the described effects can probably be attributed to the direct action of RA on these progenitors; single progenitor (CD34+) cell liquid cultures further prove this point.