期刊
ONCOTARGET
卷 8, 期 47, 页码 81794-81802出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.20864
关键词
DLBCL; PI3K; Idelalisib; ABC DLBCL; BYL719
资金
- National Institutes of Health, National Cancer Institute
Cell line models of the activated B cell-like (ABC) subtype of diffuse large B cell (DLBCL) depend on both NF-kappa B and phosphatidylinositol 3-kinase (PI3K) signaling pathways for survival, especially those with gain-of-function B cell receptor (BCR) mutations. Here we show that these cells depend specifically on the PI3K delta isoform, but that PI3K pathway interruption by PI3K delta inhibitors is short-lived due to feedback activation of the PI3K alpha isoform. PI3K delta and PI3K alpha inhibition cooperated in killing ABC DLBCL lines, and genetic knockdown of PI3K alpha sensitized cells to PI3K delta inhibition and prolonged the interruption of PI3K signaling. PI3K delta inhibition evoked feedback activation of proximal BCR signaling, which increased the association of PI3K alpha with BCAP and CD19 and increased overall PI3K activity. These results support the clinical evaluation of dual PI3K delta and PI3K alpha inhibition in patients with ABC DLBCL.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据