ERG and leukemia: Possible mechanisms of cooperation between ERG and the secondary alterations found in DS-leukemia include increased chromatin accessibility for ERG (along with RUNX1; another transcription factor encoded by chromosome 21), through the alteration of cohesin complex components [103], and molecular interplay between ERG and the RAS/MAPK pathway, in which ERG induces the transcriptional signature of RAS/MAPK activation and RAS/MAPK regulates ERG activity [104, 105].