While Tal1:E protein and Lyl1:E protein dimers have targets implicated in T-ALL (17–21), their ability to inhibit E protein homodimer formation is sufficient to promote T cell transformation as revealed by the development of T-ALL like disease in E2a-/- mice and in mice ectopically expressing inhibitors of E protein DNA binding (22–25). The gene discussed is LYL1; the disease is acute lymphoblastic leukemia.