title: BCL-2 expression does not not correlate with patient outcome in pediatric acute myelogenous leukemia.
abstract: 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.
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, California 94305, USA. naumovsk@leland.stanford.edu
authors.forename: L
authors.initials: L
authors.lastname: Naumovski
authors.forename: G
authors.initials: G
authors.lastname: Martinovsky
authors.forename: C
authors.initials: C
authors.lastname: Wong
authors.forename: M
authors.initials: M
authors.lastname: Chang
authors.forename: Y
authors.initials: Y
authors.lastname: Ravendranath
authors.forename: H
authors.initials: H
authors.lastname: Weinstein
authors.forename: G
authors.initials: G
authors.lastname: Dahl
mesh_terms: 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
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2