Myeloid differentiation in liquid cultures of cells from patients with chronic myeloid leukemia: effects of retinoic acid and indomethacin.

To study the effects of retinoic acid (RA) and indomethacin on myeloid differentiation, normal and chronic myeloid leukemic (CML) bone marrow cells lighter than 1.065 g/ml were incubated in liquid cultures and grown in agar. Retinoic acid (RA) (10(-8) M and 10(-6) M) increased the number of clusters (3-40 cells) formed in agar and also increased the neutrophil production in liquid cultures. Indomethacin (10(-6) M) did not change the cell growth in agar. In liquid culture, however, more macrophages and fewer neutrophils were produced in the presence of indomethacin. The results suggest that RA enhances neutrophil production by stimulating the proliferation and maturation of a cluster-forming cell within the myeloblast-promyelocyte compartment. The stimulatory effect of indomethacin on macrophage production is probably secondary to its inhibition of prostaglandin synthesis, which inhibits the proliferation of monocyte precursor cells. No major differences were noted between CML and normal cells in their responses to RA or indomethacin.