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Blood, 1 June 2006, Vol. 107, No. 11, pp. 4524-4531. Prepublished online as a Blood First Edition Paper on February 7, 2006; DOI 10.1182/blood-2005-08-3305. This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: 2005-08-3305v1 107/11/4524    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Meyer, L. H. Articles by Stahnke, K. Search for Related Content PubMed PubMed Citation Articles by Meyer, L. H. Articles by Stahnke, K. Related Collections Neoplasia Apoptosis Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Cytochrome c–related caspase-3 activation determines treatment response and relapse in childhood precursor B-cell ALL Lüder Hinrich Meyer, Leonid Karawajew, Martin Schrappe, Wolf-Dieter Ludwig, Klaus-Michael Debatin, and Karsten Stahnke From the Universitätsklinik für Kinder-und Jugendmedizin, University of Ulm; Helios Klinikum Berlin-Buch, Robert-Rössle-Klinik, Charité, Campus Berlin-Buch, Berlin; and Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Allgemeine Pädiatrie, Kiel, Germany. Deficient activation of apoptosis signaling pathways may be responsible for treatment failure in acute leukemia. Here, we address the impact of intact apoptosis signaling in 78 patients with pediatric precursor B-cell acute lymphoblastic leukemia (ALL) by analysis of 2 key apoptogenic events: caspase-3 activation and cytochrome c release in leukemia cells cultured in vitro. Both events correlated only in the group of patients who had a good response and patients in continuous remission, suggesting that intact apoptosis signaling is a characteristic for favorable outcome. By combining both parameters, we identified a novel indicator, cytochrome c–related activation of caspase-3 (CRAC). CRAC directly connects the extent of caspase-3 activation to cytochrome c release in single cells in an individual patient sample. In CRAC-positive patients, indicating proficient apoptosis signaling, the number of persisting leukemia cells on day 15 was significantly lower than in the CRAC-negative patient group (n = 27, mean 6.0% versus n = 36, mean 22.6%; P = .003). At a median follow-up of 31 months, disease-free survival was 84 months (95% CI = 76 to 91 months) and 66 months (95% CI = 52 to 80 months) for patients with positive and negative CRAC, respectively (P = .019). CRAC may serve as a functionally defined risk factor for treatment stratification. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. H. Meyer, M. Queudeville, S. M. Eckhoff, U. Creutzig, D. Reinhardt, L. Karawajew, W.-D. Ludwig, K. Stahnke, and K.-M. Debatin Intact apoptosis signaling in myeloid leukemia cells determines treatment outcome in childhood AML Blood, March 1, 2008; 111(5): 2899 - 2903. [Abstract] [Full Text] [PDF]

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