LEUKEMIA-ASSOCIATED RETINOIC ACID RECEPTOR-ALPHA FUSION PARTNERS, PMLAND PLZF, HETERODIMERIZE AND COLOCALIZE TO NUCLEAR-BODIES

In acute promyelocytic leukemia (APL), the typical t(15;17) and the ra re t(11;17) translocations express, respectively, the PML/RAR alpha an d PLZF/RAR alpha fusion proteins (where RAR alpha is retinoic acid rec eptor alpha). Herein, we demonstrate that the PLZF and PML proteins in teract,vith each other and colocalize onto nuclear bodies (NBs), Furth ermore, induction of PML expression by interferons leads to a recruitm ent of PLZF onto NBs without increase in the levels of the PLZF protei n, PML/RAR alpha and PLZF/RAR alpha localize to the same microspeckled nuclear domains that appear to be common targets for the two fusion p roteins in APL, Although PLZF/RAR alpha does not affect the localizati on of PML, PML/RAR alpha delocalizes the endogenous PLZF protein in t( 15;17)-positive NB4 cells, pointing to a hierarchy in the nuclear targ eting of these proteins, Thus, our results unify the molecular pathoge nesis of APL with at least two different RAR alpha gene translocations and stress the importance of alterations of PLZF and RAR alpha nuclea r localizations in this disease.