We previously reported that treating Pten-null T-ALL model mice with a PI3K inhibitor is effective only at the preleukemia stage, not after leukemia has developed (Guo et al., 2011; Blackburn et al., 2014), suggesting the importance of cotargeting the LSC ‘stemness’ maintenance pathway once LSCs have been generated. The gene discussed is PTEN; the disease is acute lymphoblastic leukemia.