SPI1 and neoplasm: Interestingly, PU.1 interacts with both RARA and PML/RARA, and while PML/RARA has been demonstrated to downregulate PU.1 [22], ATRA treatment restores PU.1 levels [22], thus suggesting a tumor suppressive role of PU.1 in APL, through the transcriptional regulation of specific downstream target genes.