Abstract 1728: Bcl-XL overexpression prevents B Cell receptor driven autophagy in IgM+ lymphoma.

Abstract

Abstract Our previous studies showed that B cell receptor (BCR) induced apoptosis in lymphoma was preceded by suppression of PI-3K [Carey GB, Scott DW (2001) J. Immunol, 166: 1618-1626]. PI-3K stimulates mTOR, a suppressor of autophagy and mitophagy. In addition, Bcl-XL is known to inhibit BCR-driven apoptosis in lymphoma, although the underlying mechanism is not clear. Therefore the present study examined autophagy in BCR induced apoptosis in lymphoma cells expressing high or low levels of Bcl-XL. WEHI-231 and WEHI-231 cells expressing Bcl-XL (WEHI-231/Bcl-XL) were treated with anti-IgM to cross-link the BCR and to determine the cellular processes leading to apoptosis. The results confirmed dramatic mitochondrial dysfunction followed by apoptosis in parental WEHI-231 compared to WEHI-231/BclXL. BCR-crosslinking resulted in a massive and rapid induction of the autophagic response in parental WEHI-231 compared to those expressing Bcl-XL. Furthermore, treatment with STF-62247, a small molecule inducer of autophagy, resulted in apoptosis in WEHI-231 but not WEHI-231/BclXL cells. These data suggest that BclXL prevents BCR-driven apoptosis in lymphoma via blocking autophagic and mitophagic responses. Hence, combinations of small molecule autophagy inducers and Bcl-XL antagonists may prove to be effective in addressing lymphoma. Supported by NCI Grant UH2CA158689 to G.B.C. Citation Format: Gregory B. Carey, Sanjit K. Roy, Alphius Sesay. Bcl-XL overexpression prevents B Cell receptor driven autophagy in IgM+ lymphoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1728. doi:10.1158/1538-7445.AM2013-1728