Objective: To make a comparison of biological properties between PML-RARalpha and PLZF-RARalpha fusion proteins.
Methods: Receptor radioligand binding assay, receptor DNA binding assay and immunofluorescence methods were used.
Results and conclusion: PML-RARalpha and PLZF-RARalpha had similar ligand-binding affinities. Both could bind in vitro to retinoic acid response elements (RAREs) forming homodimers and to retinoic acid X receptor. However ,they differed in the relative binding affinities to different RAREs,the behavior of forming complex with RXR and the subcellular localization. More importantly, PML-RARalpha and PLZF-RARalpha could block different regulatory pathways mediated by PML or PLZF, through heterocomplex formation with wild-type PML or PLZF. The differences between PML-RARalpha and PLZF-RARalpha may in part explain the apparent resistance of APL with t(11;17) to differentiating effect of all-trans retinoic acid (ATRA).