Control of apoptosis in hematopoiesis and leukemia by cytokines, tumor suppressor and oncogenes.

Hematopoietic cells require certain cytokines including colony-stimulating factors and interleukins to maintain viability. Without these cytokines the program of apoptotic cell death is activated. Cells from many myeloid leukemias require cytokines for viability, and apoptosis is also activated in these leukemic cells after cytokine withdrawal resulting in reduced leukemogenicity. The same cytokines protect normal and leukemic cells from induction of apoptosis by irradiation and cytotoxic chemotherapeutic compounds. This suggests that decreasing the levels of viability inducing cytokines may increase the effectiveness of cytotoxic anti-cancer therapy. The susceptibility of normal and cancer cells to induction of apoptosis is also regulated by the balance between apoptosis-inducing genes such as the tumor suppressor wild-type p53, and c-myc and bax, and apoptosis-suppressing genes such as the oncogene mutant p53, and bcl-2 and bcl-XL. Cell susceptibility to induction of apoptosis in leukemic cells could be enhanced by increased expression of apoptosis-inducing genes and/or decreased expression of apoptosis-suppressing genes. Modulation of expression of apoptosis-regulating genes should thus also be useful for improvement of anti-cancer therapy.