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Targeting Bcl-2 Family Proteins in Childhood Leukemia

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New Agents for the Treatment of Acute Lymphoblastic Leukemia

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Abstract

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.

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Authors and Affiliations

  1. Clinical and Experimental Pharmacology, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK

    Guy Makin

  2. School of Cancer and Enabling Sciences, University of Manchester, Manchester, UK

    Guy Makin

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  2. Caroline Dive
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  1. Christie Hospital, Dept. Paediatric & Adolescent Oncology, University of Manchester, Manchester, M20 4BX, United Kingdom

    Vaskar Saha

  2. , School of Cancer Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom

    Pamela Kearns

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Makin, G., Dive, C. (2011). Targeting Bcl-2 Family Proteins in Childhood Leukemia. In: Saha, V., Kearns, P. (eds) New Agents for the Treatment of Acute Lymphoblastic Leukemia. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-8459-3_7

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