A Bim-targeting strategy overcomes adaptive bortezomib resistance in myeloma through a novel link between autophagy and apoptosis.

@article{Chen2014ABS,
  title={A Bim-targeting strategy overcomes adaptive bortezomib resistance in myeloma through a novel link between autophagy and apoptosis.},
  author={Shuang Chen and Yu Zhang and Liang Zhou and Yun Leng and Hui Lin and Maciej Kmieciak and Xin-Yan Pei and Richard M. Jones and Robert Z. Orlowski and Yun Dai and Steven Grant},
  journal={Blood},
  year={2014},
  volume={124 17},
  pages={2687-97}
}
Bim contributes to resistance to various standard and novel agents. Here we demonstrate that Bim plays a functional role in bortezomib resistance in multiple myeloma (MM) cells and that targeting Bim by combining histone deacetylase inhibitors (HDACIs) with BH3 mimetics (eg, ABT-737) overcomes bortezomib resistance. BH3-only protein profiling revealed high Bim levels (Bim(hi)) in most MM cell lines and primary CD138(+) MM samples. Whereas short hairpin RNA Bim knockdown conferred bortezomib… CONTINUE READING
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