biostudies-literatureGary JMIntramural NIH HHSNCINCI NIH HHSNIHCenter for Cancer Research2221-2232https://www.ebi.ac.uk/biostudies/studies/S-EPMC9574474biostudies-literatureUnknown19(10)PI3K/AKT/mTOR pathway hyperactivation is frequent in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL). To model inhibition of mTOR, pre-T-cell lymphoblastic leukemia/lymphoma (pre-T LBL) tumor development was monitored in mice with T lymphocyte-specific, constitutively active AKT (Lck-MyrAkt2) that were either crossed to mTOR knockdown (KD) mice or treated with the mTOR inhibitor everolimus. Lck-MyrAkt2;mTOR KD mice lived significantly longer than Lck-MyrAkt2;mTOR wild-type (WT) mice, although both groups ultimately developed thymic pre-T LBL. An increase in survival was also observed when Lck-MyrAkt2;mTOR WT mice were treated for 8 weeks with everolimus. The transcriptional profiles of WT and KD thymic lymphomas were compared, and Ingenuity Pathway Upstream Regulator Analysis of dMolecular cancer therapeuticsHypomorphic mTOR Downregulates CDK6 and Delays Thymic Pre-T LBL Tumorigenesis.PMC9574474BC011065ZIA BC011065R01 CA77429ZIA BC011064R01 CA077429ZIA BC010008P30 CA006927P30 CA06927Z01 BC010008Chen JQZhang KEtienne MSimpson RMThaiwong TKiupel MWatson NZhang SKovalchuk ALXu JDubois WMichalowski AMSimmons JKPeat TJGamache BJMock BAGary JMGaikwad STesta JRfalseHypomorphic mTOR Downregulates CDK6 and Delays Thymic Pre-T LBL Tumorigenesis.PI3K/AKT/mTOR pathway hyperactivation is frequent in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL). To model inhibition of mTOR, pre-T-cell lymphoblastic leukemia/lymphoma (pre-T LBL) tumor development was monitored in mice with T lymphocyte-specific, constitutively active AKT (Lck-MyrAkt2) that were either crossed to mTOR knockdown (KD) mice or treated with the mTOR inhibitor everolimus. Lck-MyrAkt2;mTOR KD mice lived significantly longer than Lck-MyrAkt2;mTOR wild-type (WT) mice, although both groups ultimately developed thymic pre-T LBL. An increase in survival was also observed when Lck-MyrAkt2;mTOR WT mice were treated for 8 weeks with everolimus. The transcriptional profiles of WT and KD thymic lymphomas were compared, and Ingenuity Pathway Upstream Regulator Analysis of d2020-01-01T00:00:00Z2020 Oct2026-05-27T19:09:30.959Z2025-02-19T03:23:03.97ZS-EPMC95744743274742310.1158/1535-7163.MCT-19-067110.1158/1535-7163.mct-19-0671