APOPTOSIS IN THE HEMATOPOIETIC SYSTEM

Our previous studies have shown that haemopoietic stem cells undergo a poptotic death as a consequence of growth factor withdrawal. In this p aper we review the new data that has accumulated since this observatio n and compare it with older data from the 'pre-apoptotic' age. Models of erythropoiesis and granulopoiesis that incorporate apoptosis as a n ormal physiological process controlling homeostasis are examined. The converse to cell death is cell survival, and we describe experiments w hich suggest that haemopoietic growth factors can not only act as mito genic or differentiation stimuli but also act as survival signals. We, and others, have proposed that these growth factor-induced survival s ignals act through the membrane bound polypeptide receptors and share common features of signal transduction with proliferative responses. E nforced expression of bcl-2 in haemopoietic stem cells is able to over come apoptosis following the withdrawal of growth factor, and the cell s commit into different lineage differentiation programmes. Such cells spontaneously differentiate without cell division, suggesting a stoch astic model of haemopoiesis in which the major role of haemopoietic gr owth factors is to suppress apoptosis and act as mitogens. We review t he evidence that the underlying causes of some haematological diseases may be associated with change in the balance between cell survival an d death.