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Leuk Res. 2013 Nov;37(11):1557-64. doi: 10.1016/j.leukres.2013.08.004. Epub 2013 Aug 12.

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

Author information

1
Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany.

Abstract

TNF-α has pleiotropic effects on cell survival and apoptosis. The E3 ubiquitin ligase TRAF2 plays a crucial role for TNF-α mediated signaling since NF-κB activation by TNF-α is at least partially mediated by TRAF2. The objective of this study was to investigate whether TNF-α 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-3β. Induction of apoptosis and impaired proliferation after TNF-α exposure were observed. Co-treatment of FLT3-ITD-positive cells with the specific FLT3 inhibitor AC220 was able to overcome TNF-α resistance. Taken together, we conclude that TRAF2 plays an important role in signal transduction and survival of AML cells.

KEYWORDS:

AC220; AML; FLT3-ITD; TNF-α; TRAF2

PMID:
23998902
DOI:
10.1016/j.leukres.2013.08.004
[Indexed for MEDLINE]

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