INTERACTION OF RETINOIC ACID AND VITAMIN-D(3) ANALOGS ON HL-60 MYELOID LEUKEMIC-CELLS

Retinoic acid (RA) is an interesting agent which has been shown to induce differentiation and complete remission in patients with acute promyelocytic leukemia. 1,25-(OH)2-DELTA16-23-yne-cholecalciferol (16-23-D3) and 1,25-(OH)2-23-yne-cholecalciferol (23-D3) are vitamin D3 analogs capable of inducing differentiation of myeloid leukemic cells with little effect on either calcium absorption or mobilization. Using HL-60 myeloid leukemic cells as an in vitro model for human acute myeloid leukemia we observed an additive to synergistic interaction between RA and 16-23-D3 or 23-D3 with respect to the inhibition of cell growth and DNA synthesis, the induction of differentiation and the loss of cell clonogenicity. In addition, we observed that RA and 16-23-D3 interact additively with respect to the reduction of c-myc mRNA expression. These results suggest that RA used in combination with 16-23-D3 or 23-D3 may be an interesting chemotherapeutic regimen to evaluate in patients with acute myeloid leukemia.