CONTROL OF APOPTOSIS IN HEMATOPOIESIS AND LEUKEMIA BY CYTOKINES, TUMOR-SUPPRESSOR AND ONCOGENES

Hematopoietic cells require certain cytokines including colony-stimula ting factors and interleukins to maintain viability. Without these cyt okines the program of apoptotic cell death is activated. Cells from ma ny myeloid leukemias require cytokines for viability, and apoptosis is also activated in these leukemic cells after cytokine withdrawal resu lting in reduced leukemogenicity. The same cytokines protect normal an d leukemic cells from induction of apoptosis by irradiation and cytoto xic chemotherapeutic compounds. This suggests that decreasing the leve ls of viability inducing cytokines may increase the effectiveness of c ytotoxic anti-cancer therapy. The susceptibility of normal and cancer cells to induction of apoptosis is also regulated by the balance betwe en apoptosis-inducing genes such as the tumor suppressor wild-type p53 , and c-myc and bax, and apoptosis-suppressing genes such as the oncog ene mutant p53, and bcl-2 and bcl-X(L). Cell susceptibility to inducti on of apoptosis in leukemic cells could be enhanced by increased expre ssion of apoptosis-inducing genes and/or decreased expression of apopt osis-suppressing genes. Modulation of expression of apoptosis-regulati ng genes should thus also be useful for improvement of anti-cancer the rapy.