The role of Bcl-2 family proteins in chronic lymphocytic leukaemia.
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.
Buggins
Andrea G S
AG
Department of Haematological Medicine, King's College London, London, UK.
Pepper
Chris J
CJ
D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002463:Cell Membrane Permeability; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D018390:Gene Targeting; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051336:Mitochondrial Membranes / Q000502:physiology; D008954:Models, Biological; D005810:Multigene Family; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000145:classification / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species