Targeting Bcl-2 Family Proteins in Childhood Leukemia



The failure of apoptosis is fundamental to tumour development and contributes to pleiotropic drug resistance, especially in leukemia. The explosion of understanding of the regulation of apoptosis over the last ten years has led to the development of rationally designed therapeutics specifically targeted to components of this pathway. The multi-domain anti-apoptotic proteins Bcl-2 and Bcl-xL are critical to the engagement of the mitochondrial pathway of apoptosis after cytotoxic drug damage, acting to prevent the activation of the multi-domain pro-apoptotic proteins Bax and Bak and thus prevent the release of apoptogenic factors, including cytochrome c, smac and omi, from the mitochondrial intermembrane space. Considerable evidence has accumulated on the importance of Bcl-2 and Bcl-xL in preventing cytotoxic drug-induced apoptosis in leukemia and lymphoma models. A number of strategies have now entered clinical trials that aim to target Bcl-2 or Bcl-xL.


Mantle Cell Lymphoma Splenic Marginal Zone Lymphoma Mantle Cell Lymphoma Cell Proteasome Inhibitor Bortezomib Mitochondrial Outer Membrane Potential 
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© Springer Science+Business Media, LLC 2011 2011

Authors and Affiliations

  1. 1.Clinical and Experimental Pharmacology, Paterson Institute for Cancer ResearchUniversity of ManchesterManchesterUK
  2. 2.School of Cancer and Enabling SciencesUniversity of ManchesterManchesterUK

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