EXPRESSION OF RETINOID-X RECEPTOR A IS INCREASED UPON MONOCYTIC CELL-DIFFERENTIATION

1 alpha, 25-Dihydroxyvitamin D3 (VD) is a potent inducer of monocytic differentiation of both normal and leukemic cells. Its effects are med iated by its nuclear receptor (VDR). Efficient gene activation require s the heterodimerization of VDR with Retinoid X Receptors (RXR). In th e present study using specific antibodies, we analyzed the expression of the RXR alpha protein in blood mononuclear cells from acute myeloid patients (AML) (10 cases) and from myelomonocytic cell lines arrested at different stages of differentiation. We observed that the RXR alph a expression increased during myelomonocytic differentiation, since th e highest levels were found in AML samples and in myelomonocytic cell lines having the highest amounts of monocytic precursors. We also demo nstrated that fresh leukemic cells, whatever their stage of differenti ation, as well as myelomonocytic cell lines, respond to VD by an incre ase in RXR alpha levels. Combinations of all-trans retinoic acid (RA) and VD, in some cases, increased this effect. This response suggests t he involvement of RXR alpha in monocytic differentiation upon VD treat ment. (C) 1996 Academic Press, Inc.