The role of Bcl-2 family proteins in chronic lymphocytic leukaemia

Abstract Bcl-2 family proteins have long been implicated in the pathology of chronic lymphocytic leukaemia (CLL). Indeed, a number of these proteins have been shown to have prognostic importance in this disease. The precise ways in which these proteins impact upon CLL and the ways in which they are...

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Bibliographic Details
Published in:Leukemia research 2010-07, Vol.34 (7), p.837-842
Main Authors: Buggins, Andrea G.S, Pepper, Chris J
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacokinetics
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Apoptosis
Apoptosis - drug effects
Apoptosis - physiology
Bcl-2
Cell Membrane Permeability
Chronic lymphocytic leukaemia
Drug resistance
Drug Resistance, Neoplasm
Gene Expression Regulation, Neoplastic
Gene Targeting
Hematology, Oncology and Palliative Medicine
Humans
Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy
Leukemia, Lymphocytic, Chronic, B-Cell - metabolism
Leukemia, Lymphocytic, Chronic, B-Cell - pathology
Microenvironment
Mitochondrial Membranes - physiology
Models, Biological
Multigene Family
Neoplasm Proteins - antagonists & inhibitors
Neoplasm Proteins - physiology
Protein Structure, Tertiary
Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors
Proto-Oncogene Proteins c-bcl-2 - classification
Proto-Oncogene Proteins c-bcl-2 - physiology
Reactive Oxygen Species - metabolism
Therapeutics
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Summary:Abstract Bcl-2 family proteins have long been implicated in the pathology of chronic lymphocytic leukaemia (CLL). Indeed, a number of these proteins have been shown to have prognostic importance in this disease. The precise ways in which these proteins impact upon CLL and the ways in which they are regulated remain incompletely resolved. However, significant advances have been recently made in our understanding of how these proteins are controlled by genetic, epigenetic and microenvironmental cues. Furthermore, major progress has been made in trying to target these proteins therapeutically. Here we review the current knowledge about this family of apoptosis-regulating proteins and how they impact upon drug resistance and disease progression. We also summarise evolution in the development of Bcl-2 family inhibitors for the treatment of CLL and other cancers.
ISSN:0145-2126
1873-5835
DOI:10.1016/j.leukres.2010.03.011