Author/Authors :
Subramaniam، نويسنده , , Prem S. and Whye، نويسنده , , Dosh W. and Efimenko، نويسنده , , Evgeni and Chen، نويسنده , , Jianchung and Tosello، نويسنده , , Valeria and De Keersmaecker، نويسنده , , Kim and Kashishian، نويسنده , , Adam Harvey-Thompson Alberto Marocchino، نويسنده , , Mary Ann and Castillo، نويسنده , , Mireia and Cordon-Cardo، نويسنده , , Carlos and Davé، نويسنده , , Utpal P. and Ferrando، نويسنده , , Adolfo and Lannutti، نويسنده , , Brian J. and Diacovo، نويسنده , , Thomas G.، نويسنده ,
Abstract :
Summary
tutive phosphoinositide 3-kinase (PI3K)/Akt activation is common in T cell acute lymphoblastic leukemia (T-ALL). Although four distinct class I PI3K isoforms (α, β, γ, δ) could participate in T-ALL pathogenesis, none has been implicated in this process. We report that in the absence of PTEN phosphatase tumor suppressor function, PI3Kγ or PI3Kδ alone can support leukemogenesis, whereas inactivation of both isoforms suppressed tumor formation. The reliance of PTEN null T-ALL on the combined activities of PI3Kγ/δ was further demonstrated by the ability of a dual inhibitor to reduce disease burden and prolong survival in mice as well as prevent proliferation and promote activation of proapoptotic pathways in human tumors. These results support combined inhibition of PI3Kγ/δ as therapy for T-ALL.
