RAR fusions in classical and atypical APL response to ATRA therapy. (Top) Classic PML::RARA responds to ATRA therapy. ATRA binds the ligand binding domain (LBD), inducing a conformational change, coactivator recruitment, transactivation, and fusion protein degradation. (Bottom) The various tripartite RARA or RARG fusions with LBD-H11_12 truncations fail to bind coactivators, leading to ATRA resistance. Examples of N- or C-terminal sequences, as well as positions of the junctions, are shown.