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Prepublished online as a Blood First Edition Paper on November 7, 2002; DOI 10.1182/blood-2002-06-1714. This Article Full Text (PDF) All Versions of this Article: 2002-06-1714v1 101/6/2125    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 Del Poeta, G. Articles by Amadori, S. Search for Related Content PubMed PubMed Citation Articles by Del Poeta, G. Articles by Amadori, S. Social Bookmarking                   What's this? Submitted June 12, 2002 Accepted October 31, 2002 The amount of spontaneous apoptosis detected by bax/bcl-2 ratio predicts outcome in acute myeloid leukemia (AML) Giovanni Del Poeta*, Adriano Venditti, Maria Ilaria Del Principe, Luca Maurillo, Francesco Buccisano, Anna Tamburini, Maria Christina Cox, Annibale Franchi, Antonio Bruno, Carla Mazzone, Paola Panetta, Giovanna Suppo, Mario Masi, and Sergio Amadori Cattedra e Divisione Ematologia, University Tor Vergata, Rome, Italy * Corresponding author; email: g.delpoeta{at}tin.it. The inability to undergo apoptosis is a crucial mechanism of multidrug resistance in acute myeloid leukemia (AML) and the analysis of mitochondrial apoptotic proteins may represent a significant prognostic tool to predict outcome. Bcl-2 and bax oncoproteins were evaluated in 255 de novo AML patients (pts) by flow cytometry using an anti-bcl-2 monoclonal antibody (MoAb) and an anti-bax MoAb. The results were expressed as an index (bax/bcl-2), obtained by dividing bax mean fluorescence intensity (MFI) and bcl-2 MFI. Lower bax/bcl-2 was associated with FAB M0-M1 classes (P=0.00001) and CD34 >20% (P<0.00001). There were striking inverse correlations between CD34 or CD117 MFI and bax/bcl-2 values (r=.-40, P<0.000001 and r=-.29, P=0.000002), confirming that immaturity is consistent with this index. Moreover, lower bax/bcl-2 levels were correlated with poor risk cytogenetics (P=0.0002). A significant higher complete remission (CR) rate was found in pts with higher bax/bcl-2 (79% vs 45%; P=0.00001). Also both a longer overall survival (OS) and disease free survival (DFS) were observed in pts with higher bax/bcl-2 (P=0.00001 and =0.019). Noteworthy, bax/bcl-2 levels accurately predicted the clinical response and outcome of pts with normal or unknown cytogenetics. Indeed, within this subset of 147 pts, higher bax/bcl-2 was significantly associated both with a higher CR rate (86% vs 42%; P<0.00001) and a longer OS (P=0.0016). The independent prognostic value of bax/bcl-2 was confirmed in multivariate analysis. Therefore, mitochondrial oncoproteins, such as bcl-2 and bax, represent both sensitive indicators of clinical outcome and potential targets of novel pro-apoptotic molecules in order to circumvent chemoresistance. 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] X.-F. Huang, S.-K. Luo, J. Xu, J. Li, D.-R. Xu, L.-H. Wang, M. Yan, X.-R. Wang, X.-B. Wan, F.-M. 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