Targeting nonclassical oncogenes for therapy in T-ALL.
Cancer Cell
; 21(4): 459-72, 2012 Apr 17.
Article
en En
| MEDLINE
| ID: mdl-22516257
ABSTRACT
Constitutive phosphoinositide 3-kinase (PI3K)/Akt activation is common in T cell acute lymphoblastic leukemia (T-ALL). Although four distinct class I PI3K isoforms (α, ß, 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Purinas
/
Isoformas de Proteínas
/
Quinazolinonas
/
Leucemia-Linfoma Linfoblástico de Células T Precursoras
/
Inhibidores de las Quinasa Fosfoinosítidos-3
/
Antineoplásicos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Cell
Asunto de la revista:
NEOPLASIAS
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos