Increased sensitivity to a vitamin D3 analog in HL-60 myeloid leukemic cells resistant to all-trans retinoic acid.

All-trans retinoic acid (ATRA) has been demonstrated to induce the in vitro differentiation of human myeloid leukemic cells by several investigators. In addition, ATRA has been reported to induce complete remission in patients with acute promyelocytic leukemia. However, the majority of the patients relapse after several months of ATRA therapy. Since one possible cause of relapse in these patients is drug resistance, it is of interest to investigate the antileukemic activity of other agents that can be used in combination with ATRA in order to overcome this problem. Vitamin D3 analogs such as 1,25-dihydroxy-delta 16-23-yne-cholecalciferol (16-23-D3) are also capable of inducing differentiation of myeloid leukemic cells. In this study we have isolated a clone of HL-60 leukemic cells that is resistant to ATRA. We have observed that the resistant cell line (HL-60/RA) was more sensitive to the antileukemic action of 16-23-D3 than the parental cell line with respect to the inhibition of cell growth and DNA synthesis, the induction of differentiation and the loss of cell clonogenicity.