Bcl-2 proteins in development, health, and disease of the hematopoietic system

FEBS J. 2016 Aug;283(15):2779-810. doi: 10.1111/febs.13683. Epub 2016 Mar 21.


Members of the Bcl-2 protein family regulate cell fate decisions following a variety of developmental cues or stress signals, with the outcomes of cell death or survival, thus shaping multiple mammalian tissues. This review describes in detail how anti- and proapoptotic Bcl-2 proteins contribute to the development and functioning of the fetal and adult hematopoietic systems and how they influence the generation and maintenance of different hematopoietic lineages. An overview on how stress signals such as genotoxic stress or inflammation can compromise blood cell production, partially by engaging the intrinsic apoptosis pathway, is presented. Finally, the review describes how Bcl-2 protein deregulation-either leading to increased apoptosis resistance or excessive cell death-contributes to many hematological disorders, with specific focus on rare disorders of hematopoiesis and how this knowledge may be used therapeutically.

Keywords: BH3-only proteins; Bcl-2; apoptosis; bone marrow failure; cytopenia; erythropoiesis; hematopoiesis; megakaryopoiesis; myelopoiesis; myeloproliferation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Lineage
  • Cell Survival
  • Hematologic Diseases / etiology
  • Hematopoiesis*
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic System / embryology
  • Hematopoietic System / physiology*
  • Humans
  • Mice
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Stress, Physiological


  • Proto-Oncogene Proteins c-bcl-2