Effects of 1,25-dihydroxy vitamin D3 on all-trans retinoic acid sensitive and resistant acute promyelocytic leukemia cells.

Following challenge of the acute promyelocytic leukemia (APL) cell line, NB4, with 1, 25 dihydroxy vitamin D3 (1, 25 D3), no increase in the expression of the monocytic surface markers, CD11c, CD14 and HLA-DR is observed. By contrast, 1, 25 D3 increases the expression of CD11b, an early myeloid marker and enhances adherence to plastic following priming of the cells with phorbol 12-myristate 13-acetate (PMA). NB4.306 and NB4.007/6, two all-trans retinoic acid-resistant cell lines originated from NB4 promyelocytes and lacking expression of a complete form of PML-RAR, are totally resistant to 1, 25 D3-dependent induction of CD11b. In addition, NB4.306 cells do not show enhanced plastic adherence following treatment with the vitamin D metabolite and PMA. NB4 and NB4.306 express similar amounts of the transcripts coding for the vitamin D3 receptor and the retinoid accessory receptors, RXR alpha and RXR beta, both in basal conditions and upon treatment with 1, 25 D3.