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

The Promyelocytic leukemia–retinoic acid receptor alpha fusion protein (PML–RARα) is an abnormal chimeric oncoprotein produced by a chromosomal translocation t(15;17), which fuses part of the PML gene from chromosome 15 with part of the RARA gene from chromosome 17. This event is pathognomonic for acute promyelocytic leukemia (APL). The resulting fusion disrupts both normal tumor suppressor functions mediated by PML and transcriptional regulation mediated by RARα. The PML-RARα oncoprotein acts as a dominant-negative inhibitor that blocks myeloid cell differentiation at the promyelocyte stage, represses genes required for maturation via aberrant recruitment of co-repressors, disrupts apoptosis and senescence mechanisms, and leads to accumulation and survival of immature leukemic blasts. Treatment with all-trans retinoic acid targets this molecule directly—binding relieves its repressive effects on gene expression—enabling terminal differentiation and remission in most cases.

Other names

PML-RARaPML/RARα fusion proteinPromyelocytic leukemia protein–retinoic acid receptor alpha fusion proteint(15;17) fusion oncoprotein

ATRA binds to the RARα portion, inducing degradation or conformational change in the fusion protein, relieving transcriptional repression and allowing differentiation of leukemic cells.