AffiliationCRC Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie (NHS Trust) Hospital, Manchester, U.K.
MetadataShow full item record
AbstractOur previous studies have shown that haemopoietic stem cells undergo apoptotic death as a consequence of growth factor withdrawal. In this paper we review the new data that has accumulated since this observation and compare it with older data from the 'pre-apoptotic' age. Models of erythropoiesis and granulopoiesis that incorporate apoptosis as a normal physiological process controlling homeostasis are examined. The converse to cell death is cell survival, and we describe experiments which suggest that haemopoietic growth factors can not only act as mitogenic or differentiation stimuli but also act as survival signals. We, and others, have proposed that these growth factor-induced survival signals act through the membrane bound polypeptide receptors and share common features of signal transduction with proliferative responses. Enforced expression of bcl-2 in haemopoietic stem cells is able to overcome apoptosis following the withdrawal of growth factor, and the cells commit into different lineage differentiation programmes. Such cells spontaneously differentiate without cell division, suggesting a stochastic model of haemopoiesis in which the major role of haemopoietic growth factors is to suppress apoptosis and act as mitogens. We review the evidence that the underlying causes of some haematological diseases may be associated with change in the balance between cell survival and death.
CitationApoptosis in the haemopoietic system. 1994, 345 (1313):257-63 Philos. Trans. R. Soc. Lond., B, Biol. Sci.
JournalPhilosophical Transactions of the Royal Society of London. Series B, Biological Sciences
- Physician Education: Myelodysplastic Syndrome.
- Authors: Yoshida Y
- Issue date: 1996
- Life and death during hematopoietic differentiation.
- Authors: Opferman JT
- Issue date: 2007 Oct
- Progression of the myeloid differentiation program is dominant to transforming growth factor-beta 1-induced apoptosis in M1 myeloid leukemic cells.
- Authors: Selvakumaran M, Reed JC, Liebermann D, Hoffman B
- Issue date: 1994 Aug 15
- The role of apoptosis in the development of AGM hematopoietic stem cells revealed by Bcl-2 overexpression.
- Authors: Orelio C, Harvey KN, Miles C, Oostendorp RA, van der Horn K, Dzierzak E
- Issue date: 2004 Jun 1
- Optimal proliferation of a hematopoietic progenitor cell line requires either costimulation with stem cell factor or increase of receptor expression that can be replaced by overexpression of Bcl-2.
- Authors: Huang HM, Li JC, Hsieh YC, Yang-Yen HF, Yen JJ
- Issue date: 1999 Apr 15