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Related Collections Neoplasia Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 June 2002, Vol. 99, No. 11, pp. 4109-4115 NEOPLASIA In vitro susceptibility to dexamethasone- and doxorubicin-induced apoptotic cell death in context of maturation stage, responsiveness to interleukin 7, and early cytoreduction in vivo in childhood T-cell acute lymphoblastic leukemia Christian Wuchter, Velia Ruppert, Martin Schrappe, Bernd Dörken, Wolf-Dieter Ludwig, and Leonid Karawajew From the Department of Hematology, Oncology, and Tumor Immunology, Robert Rössle Cancer Center, Charité, Humboldt-University of Berlin, Germany; HELIOS Klinikum Berlin, Germany; and the Department of Pediatrics, Medical School of Hannover, Germany. Within childhood T-cell acute lymphoblastic leukemia (T-ALL), patients with a cortical (CD1a+) immunophenotype have been identified as a subgroup with favorable outcome in the acute lymphoblastic leukemia-Berlin-Frankfurt-Münster (ALL-BFM), Cooperative study group for childhood acute lymphoblastic leukemia (COALL) and Pediatric Oncology Group studies. We investigated in leukemic samples of children with T-ALL (n = 81) whether the different in vivo therapy response could be linked to differential in vitro susceptibility to apoptotic cell death. The extent of dexamethasone- as well as doxorubicin-induced apoptosis, detected by annexin V staining, positively correlated with the expression levels of CD1a (Spearman correlation coefficient, rs = 0.3 and 0.4, respectively; P < .01). When compared to cortical T-ALL, mature (CD1a , surface CD3+) T-ALL were significantly more resistant to doxorubicin, and immature, pro-/pre-T-ALL were more resistant to both drugs (P < .05). Apoptosis-related parameters (Bax, Bcl-2, CD95, and CD95-induced apoptosis) did not account for differential susceptibility to drug-induced apoptosis. By contrast, an interleukin 7-induced rescue of leukemic cells from spontaneous apoptosis, recently proposed to reflect distinct developmental stages and apoptotic programs in T-ALL, was highly associated with susceptibility to dexamethasone- but not doxorubicin-induced apoptosis (P < .001 versus P = .08). Analysis of clinical data showed that in vitro susceptibility to dexamethasone (but not to doxorubicin) closely correlated with early in vivo therapy response characterized by percentages of blast cells in bone marrow on day 15 (rs = 0.46, P = .001). Taken together, the in vitro assessment of drug-induced apoptosis revealed maturation-dependent differences within childhood T-ALL. The enhanced sensitivity to both drugs in cortical T-ALL might account for the better in vivo treatment response of this prognostically favorable T-ALL subgroup. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Baleydier, A.-V. Decouvelaere, J. Bergeron, P. Gaulard, D. Canioni, Y. Bertrand, S. Lepretre, B. Petit, H. Dombret, K. Beldjord, et al. T Cell Receptor Genotyping and HOXA/TLX1 Expression Define Three T Lymphoblastic Lymphoma Subsets which Might Affect Clinical Outcome Clin. Cancer Res., February 1, 2008; 14(3): 692 - 700. [Abstract] [Full Text] [PDF] S. Breit, M. Stanulla, T. Flohr, M. Schrappe, W.-D. Ludwig, G. Tolle, M. Happich, M. U. Muckenthaler, and A. E. 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	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020