Apoptosis is one mechanism by which a cell can kill itself. It is a normal, physiological process that can occur in response to numerous physiological and pathological stimuli. Survival of many cell types requires continuous signals from cytokines, and when these signals are lost, these cells undergo apoptosis. Completing the signalling pathway from cytokine receptor to apoptotic effectors is one of the holy grails of apoptosis research. A molecular understanding of the point at which a cell is irrevocably committed to die would have far reaching implications for our understanding of the role of apoptosis in human disease, because it is only those molecules that determine whether a cell commits to die that have potential to be oncogenes or tumour suppressors, and hence, therapeutic targets.

Growth and survival of haemopoietic cells is regulated by growth factors such as Interleukin-3 (IL-3). When IL-3 is removed, dependent cells kill themselves by a mechanism that can be regulated by the Bcl-2 family of apoptosis regulators, hence the term "Bcl-2-inhibitable" pathway (or "intrinsic pathway") (See Figure 1). We have generated a unique and powerful resource, a comprehensive panel of IL-3 dependent cell lines derived from gene-deleted mice lacking components of the apoptosis mechanism.

Figure 1. IL-3 signals proliferation, differentiation and survival signals in myeloid cells. Loss of IL-3 signaling leads to cell death

Figure 2. Myeloid cell lines cultured with and without IL-3