In this respect, it is important to note that there is little in vivo evidence that repression of RA target genes is sufficient to initiate APL (de The and Chen, 2010), and it is now recognized that PML-RARα also possess gain-of-function properties through its ability to bind target sequences that are not recognized by the normal RARα-RXRα heterodimers (de The and Chen, 2010). This evidence concerns the gene RARA and acute promyelocytic leukemia.