Germline mutations affecting the B cell master regulator PAX5 or the presence of the somatic ETV6-RUNX1 fusion are associated with B-ALL development in a proportion of human carriers, and this process can be faithfully recapitulated in Pax5+/− or ETV6-RUNX1 transgenic mice3,5. Here, PAX5 is linked to acute lymphoblastic leukemia.