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editorial
. 2017 Nov 12;8(59):99221–99222. doi: 10.18632/oncotarget.22385

Figure 1. Mechanism of action of ATRA and ATO in APL.

Figure 1

The PML/RARA oncoprotein induces block of myeloid differentiation and blast proliferation through i) binding at high affinity to the corepressor complex with consequent transcription repression of a number of RARA target genes; ii) PML/RARA disrupts PML nuclear bodies structure (NB). The combination of ATRA and arsenic trioxide (ATO) induces the degradation of the PML/RARA oncoprotein through the ubiquitin-proteasome pathway. PML/RARA promoter clearance induces transcriptional reactivation of target genes and nuclear bodies reformation, which ultimately induces terminal differentiation of leukemic cells.