MONOCYTIC DIFFERENTIATION OF ACUTE PROMYELOCYTIC LEUKEMIA-CELLS IN RESPONSE TO 1,25-DIHYDROXYVITAMIN D-3 IS INDEPENDENT OF NUCLEAR RECEPTOR-BINDING

We have shown that 1,25-dihydroxyvitamin D-3 (1,25 (OH)(2)D-3) primes NB4 cells, the only available acute promyelocytic leukemia cell line, for 12-O-tetradecanoylphorbol-13-acetate-induced monocytic differentiation. Here, we have used isomers of 1,25(OH)(2)D-3 to investigate the role of 1,25(OH)(2)D-3 and its putative nuclear receptor (VDR) in NB4 cell monocytic differentiation. 1 beta,25-dihydroxyvitamin D-3 (HL), a specific antagonist of only the nongenomic signals of 1,25(OH)(2)D-3 attenuated the priming effect of 1,25(OH)(2)D-3. The 6-cis conformer of 1,25(OH)(2)D-3 (HF), which is unable to bind to VDR, was 20 times more potent than 1,25(OH)(2)D-3 as a priming agent for monocytic differentiation. This response was also blocked by the HL antagonist, Unlike myelocytic HL-60 cells, which respond to 1,25(OH)(2)D-3 with increases in VDR expression and monocytic differentiation, neither HF nor 1,25(OH)(2)D-3 regulated VDR expression in NB4 cells. In the monocytic differentiation of acute promyelocytic leukemia cells, 1,25(OH)(2)D-3 appears to signal through a pathway independent of VDR/VDRE action.