Evaluation of Apaf-1 and procaspases-2, -3, -7, -8, and -9 as potential prognostic markers in acute leukemia

P. A. Svingen, J. E. Karp, S. Krajewski, Jr Mesner, S. D. Gore, P. J. Burke, J. C. Reed, Y. A. Lazebnik, S. H. Kaufmann

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

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. (C) 2000 by The American Society of Hematology.

Original languageEnglish (US)
Pages (from-to)3922-3931
Number of pages10
JournalBlood
Volume96
Issue number12
DOIs
StatePublished - Dec 1 2000

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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