PRESENCE OF A FUNCTIONAL VITAMIN-D-RECEPTOR DOES NOT CORRELATE WITH VITAMIN-D3 PHENOTYPIC EFFECTS IN MYELOID DIFFERENTIATION

Although VDR is expressed in all the acute myeloid leukemia cell popul ations studied, most of these leukemias do not exibit any phenotypic r esponse when exposed to VD. To determine whether VD resistance is rela ted to an altered VDR function,we performed an analysis of VDR express ion, phosphorylation, DNA binding capacity and transactivation activit y in several leukemic myeloid cell lines arrested at different levels of maturation. Our results indicate that VD induces a clear phenotypic effect, i.e. terminal monocytic differentiation, only in leukemic cel ls of M2/M3 (intermediate myeloblasts) and M5 (monoblasts) types but n ot in erythroid precursor cells, early leukemic myeloblasts (M0/M1 typ e) and promyelocytes (M3 type). VDR expression and function are eviden t in all the nuclear extracts obtained from the different myeloid cell lines after 12 h of VD treatment, but VD activation of monocytic diff erentiation is limited to a narrow differentiation window characterize d by the M2 type myeloid cellular context.