Effect of 1,25-dihydroxyvitamin D3 and 13-cis-retinoic acid on in vitro hematopoiesis in the myelodysplastic syndromes.

The effect of 2 X 10(-10) to 2 X 10(-7) mol/L 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) and 10(-9) to 10(-6) mol/L 13-cis-retinoic acid on in vitro differentiation and proliferation of marrow cells from patients with myelodysplastic syndrome (MDS) was assessed. Cells from 17 patients were studied by the semisolid technique, and cells from seven patients by both liquid and semisolid cultures. After incubation in liquid culture with 1,25(OH)2D3, in six of seven patients evaluated an increasing number of myeloid cells (185% to 470%) acquired the morphologic appearance of mature monocyte-macrophages, and a decrease in the number of immature myeloid cells (26% to 75%) was observed. Phagocytosis and killing of Candida albicans by monocyte-macrophages incubated with 1,25(OH)2D3 were normal and similar to those processes in untreated cells. 1,25(OH)2D3 increased the percentage of monocytes that phagocytosed C. albicans in three patients. Thirteen of 17 patients showed reduced myeloid cloning, and eight showed increased cluster formation. Cloning efficiency was significantly lower in patients with refractory anemia with excess of blasts and chronic myelomonocytic leukemia. Concentrations of 2 X 10(-9) to 2 X 10(-8) mol/L 1,25(OH)2D3 and 10(-8) to 10(-7) mol/L retinoic acid had a stimulatory effect on myeloid colony growth in five of the six patients with sideroblastic and refractory anemia, but in only two of the 11 patients with refractory anemia with excess of blasts and chronic myelomonocytic leukemia. The results indicate that the differentiation pattern of myeloid precursor cells from a subset of patients with MDS was altered by exposure to 1,25(OH)2D3.