Figure 1.

Schematic representation of the molecular mechanisms involved in acute promyelocytic leukemia (APL) pathogenesis. Promyelocytic leukemia / retinoic acid receptor α (PML/RARA) exerts dominant-negative effects on RAR/RXR-dependent transcriptional control through the recruitment of co-repressor complexes (CoR) (top) and PML nuclear bodies assembly (bottom). The direct or indirect regulation of target genes is responsible for the differentiation block, aberrant self-renewal, and impairment of autophagy and apoptosis observed in APL blasts. PML nuclear bodies disruption drives enhanced self-renewal, inhibition of DNA damage response and inhibition of senescence and apoptosis, in part by p53 inactivation.