To investigate the underlying mechanisms mediating resistance to NOTCH inhibition in Pten-null T-ALL tumor cells we performed gene expression profiling of isogenic Pten-positive and Pten-deleted leukemia lymphoblasts after acute treatment with DBZ in vivo. This analysis revealed that, while direct NOTCH1 target genes (such as Hes1, Dtx1, PtcrA, HeyL and Notch3) are effectively downregulated in both Pten-positive and Pten-deleted tumors, genetic ablation of Pten elicits a global reversal of much of the transcriptional effects of NOTCH inhibition. We performed microarray gene expression analysis of GSI treatment in isogenic Pten KO or WT NOTCH1 induced leukemias
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