How Do ATRA and Arsenic Work at the Molecular Level?
To understand how ATRA and arsenic compounds act at the molecular level in treating APL, it is first important to understand the role of the PML-RARa fusion protein in the pathogenesis of APL. Retinoids that are crucial for normal myeloid differentiation act via RA receptors (RARs) and retinoid X receptors (RXRs). These belong to the steroid/thyroid/retinoid nuclear receptor superfamily of ligand-inducible transcription factors. Both RAR and RXR families consist of three subtypes: α, β, and γ [20]. RARα forms a heterodimer with RXR and binds to RA response element to control the expression of target genes in the presence of physiological concentrations (10−9–10−8 M) of retinoids (Figure 3A).
