In 203 nonsilent PAX5 mutations identified from 1,988 B-ALL cases (16), around three quarters are missense mutations enriched in the DNA-binding domain and are predicted to impair DNA binding by structural modelling, whereas disruptive mutations such as frameshift and nonsense are often found in the transcriptional regulatory domain (1, 16). Here, PAX5 is linked to precursor B-cell acute lymphoblastic leukemia.