PML/ RARA variants and their role in Arsenic Trioxide resistance in APL: a scoping review

Currently, the treatment of Acute Promyelocytic Leukemia (APL) is grounded on therapeutic regimens based on arsenic trioxide (ATO). However, mutations in the PML component of the PML/RARA oncoprotein are believed to be involved in the mechanism of resistance to this agent. We performed a scoping review to understand the role of variant PML/RARA fusion proteins in the mechanism of resistance in APL. Applying the defined criteria, we selected 10 studies, in which patients presented a picture of relapse and/or resistance after the administration of ATO, having been identified at least one PML mutation. We also reported that RARA is the most frequently mutated gene, although we also found mutations in genes related to other processes involved in cell differentiation. Briefly, this is a multifactorial mechanism and PML/RARA variants are important but not an obligatory condition for ATO resistance to occur.