Promyelocytic leukemia protein–retinoic acid receptor alpha fusion protein (PML–RARα)

PML–RARα is a fusion protein resulting from a chromosomal translocation t(15;17) that joins the promyelocytic leukemia gene (PML) on chromosome 15 to the retinoic acid receptor alpha gene (RARA) on chromosome 17. This fusion protein functions as an oncogenic transcription factor, abnormally repressing retinoic acid–responsive genes and blocking myeloid differentiation, which is the molecular hallmark of acute promyelocytic leukemia (APL)[1][3]. PML–RARα acts as a constitutive repressor of transcription, recruiting corepressor complexes and histone deacetylases; this repression is relieved on exposure to pharmacological doses of all-trans retinoic acid, which restores differentiation of leukemia cells. The presence of the PML–RARα fusion gene is diagnostic for APL and provides a highly effective therapeutic target for retinoids and arsenic trioxide therapy[1][3][4].

Other names

PML–retinoic acid receptor alpha fusion proteinPML/RARαt(15;17) fusion proteinPML-RARAPromyelocytic leukemia–retinoic acid receptor alpha fusion

Ligand-induced activation (by ATRA) overcomes dominant repression, leading to degradation of the fusion protein and induction of differentiation in leukemic promyelocytes; Arsenic trioxide induces degradation of PML–RARα, promoting apoptosis and differentiation