1-ALPHA,25-DIHYDROXYVITAMIN D-3 AND PHORBOL ESTER MEDIATE THE EXPRESSION OF ALKALINE-PHOSPHATASE IN NB4 ACUTE PROMYELOCYTIC LEUKEMIA-CELLS

Both 1 alpha,25-dihydroxyvitamin D-3 [1 alpha,25(OH)(2)D-3] and phorbo l 12-myristate 13-acetate [PMA] are cytodifferentiation agents regulat ing myeloid cell line differentiation along the monocyte/macrophage pa thway. Alkaline phosphatase (ALP) activity has been reported to be abs ent or present at low levels in monocytes/macrophages. In the present study, the acute promyelocytic leukemia cell line (NB4) was found to u ndergo monocyte/macrophage differentiation and strongly express ALP ac tivity after exposure to the combination of 1 alpha,25(OH)(2)D-3 and P MA treatment. The ALP stimulation was both dose- and time-dependent wi th the ED50 doses for 1 alpha,25(OH)(2)D-3 and PMA at 2 x 10(-10) M an d 4 x 10(-11) M, respectively. Assessment of the cell morphology via c ell adherence, phagocytosis and ALP staining confirmed that NB4 cells treated by 1 alpha,25(OH)(2)D-3 plus PMA showed macrophage characteris tics, but were also strongly stained with ALP. The present study is th e first report that NB4 cells express ALP activity as a consequence of combination treatment with 1 alpha,25(OH)(2)D-3 and PMA. (C) 1998 Pub lished by Elsevier Science Ltd. All rights reserved.