期刊
BLOOD
卷 119, 期 8, 页码 1897-1900出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-10-386763
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GS-1101 (CAL-101) is an oral PI3K delta-specific inhibitor that has shown preclinical and clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. To investigate the potential role of PI3K delta in Hodgkin lymphoma (HL), we screened 5 HL cell lines and primary samples from patients with HL for PI3K delta isoform expression and constitutive PI3K pathway activation. Inhibition of PI3K delta by GS-1101 resulted in the inhibition of Akt phosphorylation. Cocultures with stroma cells induced Akt activation in HL cells, and this effect was blocked by GS-1101. Conversely, production of the stroma-stimulating chemokine, CCL5, by HL cells was reduced by GS-1101. GS-1101 also induced dose-dependent apoptosis of HL cells at 48 hours. Reductions in cell viability and apoptosis were enhanced when combining GS-1101 with the mTOR inhibitor everolimus. Our findings suggest that excessive PI3K delta activity is characteristic in HL and support clinical evaluation of GS-1101, alone and in combination, as targeted therapy for HL. (Blood. 2012;119(8):1897-1900)
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