PTEN and acute lymphoblastic leukemia: In pre-clinical models, Guo et al. reported that the long-term treatment (3–4 months) of pre-leukemic PTEN-deleted mice with the mTOR inhibitor rapamycin blocked the LSC self-renewal and prevented disease development.98 Schubbert et al. demonstrated that treating mice engrafted with PTEN-null T-ALL cells with a combination of rapamycin and the MYC inhibitor JQ1 resulted in marked reduction of splenomegaly and significantly decreases in leukemia burden within seven days.