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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 15, 2005 Accepted January 23, 2006 Cytochrome c related caspase-3 activation determines treatment response and relapse in childhood precursor B-cell ALL Luder H Meyer, Leonid Karawajew, Martin Schrappe, Wolf-Dieter Ludwig, Klaus-Michael Debatin, and Karsten Stahnke* Universitatsklinik fur Kinder- und Jugendmedizin, University of Ulm, Ulm, Germany HELIOS Klinikum Berlin-Buch, Robert-Rossle-Klinik, Charite, Campus Berlin-Buch, Berlin, Germany Universitatsklinikum Schleswig-Holstein, Campus Kiel, Klinik fur Allgemeine Padiatrie, Kiel, Germany * Corresponding author; email: karsten.stahnke{at}uniklinik-ulm.de. 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 ALL by analysis of two key apoptogenic events: caspase-3 activation and cytochrome c release in leukemia cells cultured in vitro. Both events correlated only in the group of good responding patients and pa-tients in continuous remission suggesting that intact apoptosis signaling is character-istic for favorable outcome. By combining both parameters, we identified a novel indicator, cytochrome c related activation of capase-3 (CRAC). CRAC directly connects the extent of caspase-3 activation to cytochrome c release in single cells in an indi-vidual 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= 0.003). 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= 0.019). 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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