Bcl-2-family proteins and hematologic malignancies: history and future prospects

Blood. 2008 Apr 1;111(7):3322-30. doi: 10.1182/blood-2007-09-078162.


BCL-2 was the first antideath gene discovered, 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 antiapoptotic proteins, 3 structurally similar proapoptotic proteins, and several structurally diverse proapoptotic interacting proteins that operate as upstream agonists or antagonists. Bcl-2-family proteins regulate all major types of cell death, including apoptosis, necrosis, and autophagy. 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 established by studies of Bcl-2, representing a major step forward in current understanding of tumorigenesis. Experimental therapies targeting Bcl-2 family mRNAs or proteins are currently in clinical testing, raising hopes that a new class of anticancer drugs may be near.

Publication types

  • Historical Article
  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Cell Death
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / metabolism*
  • Drug Delivery Systems / methods
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Inhibitor of Apoptosis Proteins / antagonists & inhibitors
  • Inhibitor of Apoptosis Proteins / history
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Lymphoma, B-Cell / drug therapy
  • Lymphoma, B-Cell / history
  • Lymphoma, B-Cell / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / history
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / antagonists & inhibitors
  • RNA, Neoplasm / metabolism


  • Antineoplastic Agents
  • Inhibitor of Apoptosis Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • RNA, Neoplasm