Combined inhibition of PI3K δ and FLT3 signaling exerts synergistic antitumor activity and overcomes acquired drug resistance in FLT3-activated acute myeloid leukemia

In this report, we demonstrate that combined inhibition of PI3Kδ and FLT3 exerts synergistic antitumor activity in FLT3-activated AML. Synergistic antiproliferative effect s were observed in FLT3-activated MV-4-11 and EOL-1 AML cell lines, but not in FLT3-independent RS4;11 and HEL cells, as demonstrated by both pharmacological inhibition and silencing of PI3Kδ/FLT3. Combined treatment with PI3Kδ and FLT3 inhibitors more effectively inhibited AKT and ERK phosphoryla tion, and induced apoptosis more efficiently than either agent alone.

Source: Cancer Letters - February 3, 2018 Category: Cancer & Oncology Authors: Ye He, Liping Sun, Yongping Xu, Li Fu, Yun Li, Xubin Bao, Haoyu Fu, Chengying Xie, Liguang Lou Tags: Original Articles Source Type: research