BCL-2 EXPRESSION AND GLUCOCORTICOID-INDUCED APOPTOSIS OF LEUKEMIC ANDLYMPHOMA-CELLS

The lytic response of lymphoid cells to glucocorticoid hormones (GC) i s prototypical of the induction of apoptosis: a special form of cellul ar demise for the removal of unwanted or redundant cells. Initiation a nd execution of a death programme are therefore major checkpoints in G C-sensitivity. Although Bcl-2 protein can prevent or delay apoptosis o f lymphoma and leukemia cells, exposed to multiple cytotoxic agents, i ts antagonism of GC-induced apoptosis appears most critical in conferr ing resistance to corticosteroids. Moreover, Bcl-2 may modulate GC-sig nalling to apoptosis through its association with fundamental cellular processes such as energy state, Ca2+ homeostasis and transmembrane tr ansport. However, this signalling pathway can also be interrupted by B cl-2-independent mechanisms. This review discusses the various cellula r and oncogenetic factors that control GC sensitivity of leukemia/lymp homa cells and proposes a hypothesis of how GC may induce a death prog ramme, sensitive to blockade by Bcl-2.