The E3 ubiquitin ligase TRAF2 can contribute to TNF-α resistance in FLT3-ITD-positive AML cells

被引：14

作者：

Schnetzke, Ulf ^{[1
]}

Fischer, Mike ^{[1
]}

Spies-Weisshart, Baerbel ^{[1
]}

Zirm, Elisabeth ^{[1
]}

Hochhaus, Andreas ^{[1
]}

Mueller, Joerg P. ^{[2
]}

Scholl, Sebastian ^{[1
]}

机构：

[1] Univ Klinikum Jena, Klin Innere Med 2, Abt Hamatol Onkol, D-07740 Jena, Germany

[2] Univ Klinikum Jena, Ctr Mol Biomed, Inst Mol Zellbiol, D-07740 Jena, Germany

来源：

LEUKEMIA RESEARCH | 2013年 / 37卷 / 11期

关键词：

AML; TNF-alpha; TRAF2; FLT3-ITD; AC220; ACUTE MYELOID-LEUKEMIA; TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; INTERNAL TANDEM DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; CONSTITUTIVE ACTIVATION; FLT3; GENE; APOPTOSIS; RECEPTOR; PATHWAY;

D O I：

10.1016/j.leukres.2013.08.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

TNF-alpha has pleiotropic effects on cell survival and apoptosis. The E3 ubiquitin ligase TRAF2 plays a crucial role for TNF-alpha mediated signaling since NF-kappa B activation by TNF-alpha is at least partially mediated by TRAF2. The objective of this study was to investigate whether TNF-alpha can induce apoptosis in FLT3-ITD-positive AML cells and to elucidate the influence of TRAF2. Stable lentiviral mediated down-regulation of TRAF2 resulted in a decrease of phosphorylation of the anti-apoptotic protein AKT and its downstream target GSK-3 alpha. Induction of apoptosis and impaired proliferation after TNF-alpha exposure were observed. Cotreatment of FLT3-ITD-positive cells with the specific FLT3 inhibitor AC220 was able to overcome TNF-alpha resistance. Taken together, we conclude that TRAF2 plays an important role in signal transduction and survival of AML cells. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：1557 / 1564

页数：8

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