P53-independent responses to CX-5461 in acute lymphoblastic leukemia (ALL), human ovarian cancer models and human immortalized fibroblasts were shown to involve a G2/M checkpoint arrest and cell death via the ATM/ ATR kinase pathways.43,292,297,298 In addition to inhibiting Pol I transcription, CX-5461 was shown to induce perturbations in rDNA chromatin and replication stress, triggering non-canonical activation of ATM/ATR kinase signaling within the nucleoli. This evidence concerns the gene ATM and acute lymphoblastic leukemia.