Therefore, combining POL5551 with newer targeted agents, such as inhibitors of BRD4 [36] or DOT-1L [37] in MLL-R leukemias and phosphoinositide 3-kinase (PI3K) and mTOR inhibitors in hypodiploid ALL [38] and Philadelphia chromosome-like ALL, [39] may improve outcome in these high-risk pediatric leukemias. Here, DOT1L is linked to acute lymphoblastic leukemia.