2012
DOI: 10.1182/blood.v120.21.1625.1625
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Inhibition of Autophagy by Chloroquine Sensitises Lymphoma Cells to ABT-737-Induced Apoptosis

Abstract: 1625 Diffuse large B-cell lymphoma (DLBCL) is characterised by overexpression of the anti-apoptotic protein Bcl-2. It has been recently observed that Bcl-2 also inhibits autophagy by binding and sequestering Beclin-1, an essential autophagy protein, but it is unclear whether Bcl-2 inhibits both apoptosis and autophagy in DLBCL cells. We aimed to determine the dual role of Bcl-2 in both apoptosis and autophagy in Bcl-2 positive cell lines (Su-DHL4 and CRL) and Bcl-2 negative cell lines (Su-DHL8 a… Show more

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“…Based on recently communicated data that IL-6 treatment results in the phosphorylation of Bim at serine 69 and subsequent increases binding of Bim to Mcl-1, it is however still possible that PPP sensitizes MM cells to ABT-737 by post-translational modification of Mcl-1 and/or Bim thus inhibiting protein-protein binding [ 42 ]. In addition, both in MM and Bcl-2 diffuse large B-cell lymphoma ABT-737 was reported to induce autophagy and this ABT-737-induced autophagy was cytoprotective [ 43 , 44 ]. Consequently, disruption of autophagy by chloroquine sensitized cells to ABT-737 and this event was accompanied with a clear increase in Bim expression in MM.…”
Section: Discussionmentioning
confidence: 99%
“…Based on recently communicated data that IL-6 treatment results in the phosphorylation of Bim at serine 69 and subsequent increases binding of Bim to Mcl-1, it is however still possible that PPP sensitizes MM cells to ABT-737 by post-translational modification of Mcl-1 and/or Bim thus inhibiting protein-protein binding [ 42 ]. In addition, both in MM and Bcl-2 diffuse large B-cell lymphoma ABT-737 was reported to induce autophagy and this ABT-737-induced autophagy was cytoprotective [ 43 , 44 ]. Consequently, disruption of autophagy by chloroquine sensitized cells to ABT-737 and this event was accompanied with a clear increase in Bim expression in MM.…”
Section: Discussionmentioning
confidence: 99%