BCL-2 expression does not not correlate with patient outcome in pediatric acute myelogenous leukemia.
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.
Naumovski
L
L
Department of Pediatrics, Stanford University School of Medicine, California 94305, USA. naumovsk@leland.stanford.edu
Martinovsky
G
G
Wong
C
C
Chang
M
M
Ravendranath
Y
Y
Weinstein
H
H
Dahl
G
G
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D016896:Treatment Outcome
D019253:Proto-Oncogene Proteins c-bcl-2