In this issue of EMBO Molecular Medicine, Rehe et al (2013) build on earlier work in which they demonstrated that in high-risk B-ALL, leukemogenic potential was retained in CD34+/CD19− (the least mature subset as judged by immunophenotype), CD34+/CD19+ and CD34−/CD19+ populations (le Viseur et al, 2008). The gene discussed is CD19; the disease is precursor B-cell acute lymphoblastic leukemia.