Abstract
In normal thymus and bone marrow, a large number of unwanted lymphocytes (cells which failed to rearrange antigen receptor genes or which acquired autoreactivity) are rapidly eliminated by programmed cell death (apoptosis) in situ. Since leukemic cells are derived from these organs, knowledge of the regulation of apoptosis is important to understand leukemogenesis and also to establish a new treatment of leukemia. When leukemic cells are cultured in vitro, most of the cells die by apoptosis unless these cells are placed on bone marrow stromal cells. Although cell-to-cell contact is needed, the bone marrow microenvironment may provide some essential factors to support cell survival like colony stimulating factors for cytokine-dependent cell lines. The role of bcl-2 is to block apoptosis in peripheral lymphoid organs and also in B-cell diseases such as follicular lymphoma. Recently, other bcl-2 related proteins, such as bcl-x and bax were discovered. Virtually all the cytotoxic agents and irradiation kill leukemic cells by induction of apoptosis. Some molecules such as p53, c-myc, bcl-2 and c-jun are known to modulate the process of apoptosis, however, the exact cellular mechanism is still unknown. Biologic response modifiers such as interleukins and some ligands to the cellular antigens like Fas are also involved in the process of apoptosis. The future direction of leukemia research should focus on the molecular events of apoptosis. The method of detecting apoptosis is also mentioned.
