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13-Bcl-2 - From www.bloodjournal.org at UNIV NORTH CAROLINA...

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doi:10.1182/blood-2007-09-078162 2008 111: 3322-3330 John C. Reed prospects Bcl-2family proteins and hematologic malignancies: history and future http://bloodjournal.hematologylibrary.org/cgi/content/full/111/7/3322 Updated information and services can be found at: (34 articles) ASH 50th Anniversary Reviews collections: Blood Articles on similar topics may be found in the following http://bloodjournal.hematologylibrary.org/misc/rights.dtl#repub_requests Information about reproducing this article in parts or in its entirety may be found online at: http://bloodjournal.hematologylibrary.org/misc/rights.dtl#reprints Information about ordering reprints may be found online at: http://bloodjournal.hematologylibrary.org/subscriptions/index.dtl Information about subscriptions and ASH membership may be found online at: . Hematology; all rights reserved Copyright 2007 by The American Society of 200, Washington DC 20036. semimonthly by the American Society of Hematology, 1900 M St, NW, Suite Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published For personal use only. at UNIV NORTH CAROLINA on March 6, 2009. www.bloodjournal.org From
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Bcl-2–family proteins and hematologic malignancies: history and future prospects John C. Reed 1 1 Burnham Institute for Medical Research, La Jolla, CA BCL-2 was the first antideath gene dis- covered, a milestone that effectively launched a new era in cell death research. Since its discovery more than 2 decades ago, multiple members of the human Bcl-2 family of apoptosis-regulating proteins have been identified, including 6 antiapop- totic proteins, 3 structurally similar pro- apoptotic proteins, and several structur- ally diverse proapoptotic interacting proteins that operate as upstream ago- nists or antagonists. Bcl-2–family pro- teins regulate all major types of cell death, including apoptosis, necrosis, and auto- phagy. As such, they operate as nodal points at the convergence of multiple pathways with broad relevance to biology and medicine. Bcl-2 derives its name from its original discovery in the context of B-cell lymphomas, where chromosomal translocations commonly activate the BCL-2 protooncogene, endowing B cells with a selective survival advantage that promotes their neoplastic expansion. The concept that defective programmed cell death contributes to malignancy was es- tablished by studies of Bcl-2, represent- ing a major step forward in current under- standing of tumorigenesis. Experimental therapies targeting Bcl-2 family mRNAs or proteins are currently in clinical test- ing, raising hopes that a new class of anticancer drugs may be near. (Blood. 2008;111:3322-3330) © 2008 by The American Society of Hematology Introduction Cell death can be either physiologic or pathologic. Although medicine focused on pathologic cell death for centuries, it was the discovery of programmed cell death that breathed new life into the field of cell death research, as well as sparking major advances in multiple areas of physiology and medicine. Physi- ologic cell death in animal species generally occurs through a
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