Targeting Class I PI3Ks in the Treatment of T-cell Acute Lymphoblastic Leukemia
Abstract
This research project aims to evaluate the antileukemic activity of inhibiting the PI3K pathway in T-cell acute lymphoblastic leukemia (T-ALL) using genetic models and pharmacologic approaches. In this project we have established a broad panel of primary T-ALL cultures and primary xenograft models of human T-ALL as experimental therapeutic platform (Aim 3 Task1). In in vitro evaluation of the activity of the CAL130 inhibitor in primary T-ALL cells demonstrated significant antileukemic effects of this drug (Aim 3, Task 2). We have performed an initial evaluation of the efficacy of CAL130 treatment in T-ALL cells xenografted in immunodeficient mice (Aim 3, task 3) and analysis of the impact of PTEN and NOTCH mutations in CAL130 response (Aim 3 Task 6). Finally we have established a synergistic effect between the inhibition of the PI3K-AKT pathway and glucocorticoid therapy in vitro (Aim 3 Task 4)and in vivo (Aim 3 Task 5). Overall these results highlight the role of the PI3K pathway as therapeutic target for the treatment of T-ALL and warrant the clinical testing of PI3K inhibitors alone and in combination with glucocorticoids in the clinic.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2013
- Accession Number
- ADA591435
Entities
People
- Adolfo A. Ferrando
Organizations
- Columbia University