Pathogenesis of acute promyelocytic leukaemia (APL). The formation of various PML::RARA complexes due to the translocation between chromosomes 15 and 17 t(15;17)(q24;q21), which bind to the retinoic acid response element (RARE). The binding of PML::RARA to RARE leads to the recruitment of co-repressors and methylating enzymes (e.g., DNMT1 (DNA (cytosine-5)-methyltransferase 1) and DNMT3A), resulting in epigenetic silencing, inhibition of granulocyte differentiation, accumulation of abnormal promyelocytes and increasing self-renewal. Formation of PML::RARA complexes also inhibits normal functions of PML and RARA such that PML is unable to cause cell apoptosis and tumour suppression via nuclear body (NB) formation. RARα ability to allow localization with RxRα resulting in transcriptional differentiation.