Vitamin D compounds. Effect on clonal proliferation and differentiation of human myeloid cells

We examined the effect of 1α,25-dihydroxyvitamin D₃ (1α,25(OH)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, M1) were induced to differentiate and were inhibited in their clonal growth by exposure to 1α,25(OH)₂D₃ (50% inhibition, 3 x 10^-8-8 x 10^-10 M). A fluorinated analog of vitamin D was 5-10-fold more potent than 1α,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 1α,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 1α,25(OH)₂D₃. Our results suggest that 1α,25(OH)₂D₃ may be a cofactor in hematopoiesis and that vitamin D analogs may have a differential effect on normal versus leukemic growth.