BCL-2 DELAY OF ALKYLATING AGENT-INDUCED APOPTOTIC DEATH IN A MURINE HEMATOPOIETIC STEM-CELL LINE

Many cytotoxic agents kill cells by invoking a specific death pathway termed physiological cell death, or apoptosis. Treatment of a murine hemopoietic stem cell line, FDCP-mix, with methylmethanesulfonate (MMS) or N'-methyl-N'-nitrosourea (MNU) leads to death by apoptosis. Retroviral gene transfer was used to overexpress the bcl-2 oncogene in FDCP-mix cells, and this was associated with a delay in apoptosis in these cells after treatment with MNU and MMS and decreased sensitivity of colony formation to the cytotoxic effects of MMS. These data suggest an explanation for the refractory nature of bcl-2-expressing follicular lymphoma to cytotoxic chemotherapy and furthermore suggest that DNA-damaging antitumor therapy may contribute to the progression of disease. (C) 1994 Wiley-Liss, Inc.