Vitamin D Compounds

We examined the effect of la,25-dihydroxyvitamin D3 (la,25(0H)2D3) and a variety of vitamin D analogs on proliferation and differentiation of normal and leukemic myeloid clonogenic cells. Only cells from myeloid leukemic lines that contained relatively mature cells (HL-60, U937, THP, HEL, Ml) were induced to differentiate and were inhibited in their clonal growth by exposure to la,25(0H)hD (50% inhibition, 3 X 10-88 X 10-1O M). A fluorinated analog of vitamin D was 5-10-fold more potent than la,25(OH)2D3. Cells from a human myeloblast line (KG-1) and normal human granulocyte-monocyte stem cells (GM-CFC), both of which depend on colony-stimulating factor (CSF) for clonal growth, were stimulated in their clonal proliferation by la,25(OH)2D3 in the presence of suboptimal concentrations of CSF. Leukemic cells from 10 of 14 patients with myeloid leukemia, but not normal GM-CFC from 12 patients in remission, were markedly inhibited in their clonal proliferation by la,25(0H)2D3. Our results suggest that la,25(OH)2D3 may be a cofactor in hematopoiesis and that vitamin D analogs may have a differential effect on normal versus leukemic growth.