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. This evidence concerns the gene PTEN and Splenomegaly.