biostudies-literatureTan YNCI NIH HHS580-8https://www.ebi.ac.uk/biostudies/studies/S-EPMC4622865biostudies-literatureUnknown16(4)Constitutive activation of AKT is a frequent occurrence in the development of human T-cell acute lymphocytic leukemia/lymphomas (T-ALLs), due largely to inactivation of PTEN. Up regulation of MYC is also commonly observed in human T-ALLs. We previously demonstrated that expression of a constitutively active form of Lck-Akt2 alone is sufficient to initiate T-cell lymphoma in mice, and that tumor formation typically requires up regulation of Myc or Dlx5 caused by specific chromosomal rearrangements. Furthermore, Lck-Dlx5 mice develop T-ALLs that consistently acquire overexpression of Myc and activation of Akt, the latter due to loss of Pten expression. Proliferation of T-ALL cells from Lck-Dlx5 mice was found to be highly sensitive to the Akt pathway inhibitors BEZ235 and RAD001, as well as Cancer biology & therapyCo-targeting of Akt and Myc inhibits viability of lymphoma cells from Lck-Dlx5 mice.PMC4622865CA06927CA077429CA083638P30 CA006927Ito TKTan YKadariya YPei JSementino ETesta JRfalseCo-targeting of Akt and Myc inhibits viability of lymphoma cells from Lck-Dlx5 mice.Constitutive activation of AKT is a frequent occurrence in the development of human T-cell acute lymphocytic leukemia/lymphomas (T-ALLs), due largely to inactivation of PTEN. Up regulation of MYC is also commonly observed in human T-ALLs. We previously demonstrated that expression of a constitutively active form of Lck-Akt2 alone is sufficient to initiate T-cell lymphoma in mice, and that tumor formation typically requires up regulation of Myc or Dlx5 caused by specific chromosomal rearrangements. Furthermore, Lck-Dlx5 mice develop T-ALLs that consistently acquire overexpression of Myc and activation of Akt, the latter due to loss of Pten expression. Proliferation of T-ALL cells from Lck-Dlx5 mice was found to be highly sensitive to the Akt pathway inhibitors BEZ235 and RAD001, as well as 2015-01-01T00:00:00Z20152025-04-29T10:55:43.972Z2019-03-27T02:00:52ZS-EPMC46228652579366310.1080/15384047.2015.1018495