Svingen, P. A., Karp, J. E., Krajewski, S., Mesner, P. W., Gore, S. D., Burke, P. J., Reed, J. C., Lazebnik, Y. A., Kaufmann, S. H. (2000) Evaluation of Apaf-1 and procaspases-2, -3, -7, -8, and -9 as potential prognostic markers in acute leukemia. Blood, 96 (12). pp. 3922-3931. ISSN 0006-4971
Abstract
Recent studies have suggested that variations in levels of caspases, a family of intracellular cysteine proteases, can profoundly affect the ability of cells to undergo apoptosis. In this study, immunoblotting was used to examine levels of apoptotic protease activating factor-1 (Apaf-1) and procaspases-2, -3, -7, -8, and -9 in bone marrow samples (at least 80% leukemia) harvested before chemotherapy from adults with newly diagnosed acute myelogenous leukemia (AML, 42 patients) and acute lymphocytic leukemia (ALL, 18 patients). Levels of each of these polypeptides varied over a more than 10-fold range between specimens. In AML samples, expression of procaspase-2 correlated with levels of Apaf-1 (R(s) = 0.52, P <.02), procaspase-3 (R(s) = 0.56, P <.006) and procaspase-8 (R(s) = 0.64, P <.002). In ALL samples, expression of procaspases-7 and -9 was highly correlated (R(s) = 0.90, P <.003). Levels of these polypeptides did not correlate with prognostic factors or response to induction chemotherapy. In further studies, 16 paired samples (13 AML, 3 ALL), the first harvested before induction therapy and the second harvested at the time of leukemia regrowth, were also examined. There were no systematic alterations in levels of Apaf-1 or procaspases at relapse compared with diagnosis. These results indicate that levels of initiator caspases vary widely among different leukemia specimens but cast doubt on the hypothesis that this variation is a major determinant of drug sensitivity for acute leukemia in the clinical setting. (Blood. 2000;96:3922-3931)
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Acute Disease Adolescent Adult Aged Antineoplastic Combined Chemotherapy Protocols Apoptotic Protease-Activating Factor 1 Bone Marrow Cells Caspases Cohort Studies Enzyme Precursors HL-60 Cells Humans Immunoblotting Leukemia Leukemia, Myeloid Middle Aged Precursor Cell Lymphoblastic Leukemia-Lymphoma Prognosis Proteins Tumor Markers, Biological |
| Subjects: | diseases & disorders > cancer organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis diseases & disorders > cancer > cancer types > leukemia |
| CSHL Authors: | |
| Communities: | CSHL labs > Labeznik lab |
| Depositing User: | Matt Covey |
| Date: | 2000 |
| Date Deposited: | 12 Dec 2012 17:31 |
| Last Modified: | 12 Dec 2012 17:31 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/26388 |
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