Although the Bcl-2 protein inhibits apoptosis (programmed cell death) of lymphoid cells induced by a variety of stimuli, its effects on myeloid cell short- and long-term survival after chemotherapy are less defined. We sought to elucidate the short- and long-term effect of Bcl-2 in a well-studied myeloid cell line (HL-60) treated with specific anti-AML chemotherapy. HL-60 cells overexpressing Bcl-2 (HL-60/BCL-2) were more resistant than parental HL-60 cells to multiple chemotherapeutic agents in short-term apoptosis and viability assays. Significantly, HL-60/BCL-2 cells retained greater long-term proliferative capacity than HL-60 cells when treated with low doses of doxorubicin. To assess the importance of Bcl-2 expression in pediatric AML we correlated clinical outcome and levels of Bcl-2 protein in 22 patient specimens. The correlation did not achieve statistical significance with patient response to chemotherapy or long-term outcome, suggesting that analysis of larger numbers of patient samples would not be useful. Our study suggests that although Bcl-2 clearly promotes short and long-term survival in a myeloid cell line, measurement of Bcl-2 levels alone are not sufficient to be of prognostic significance in pediatric AML.