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Blood, 15 January 2005, Vol. 105, No. 2, pp. 821-826. Prepublished online as a Blood First Edition Paper on September 23, 2004; DOI 10.1182/blood-2004-04-1552. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: 2004-04-1552v1 105/2/821    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 Cario, G. Articles by Schrappe, M. Search for Related Content PubMed PubMed Citation Articles by Cario, G. Articles by Schrappe, M. Related Collections Neoplasia Gene Expression Genomics Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Distinct gene expression profiles determine molecular treatment response in childhood acute lymphoblastic leukemia Gunnar Cario, Martin Stanulla, Bernard M. Fine, Oliver Teuffel, Nils v. Neuhoff, André Schrauder, Thomas Flohr, Beat W. Schäfer, Claus R. Bartram, Karl Welte, Brigitte Schlegelberger, and Martin Schrappe From the Department of Pediatric Hematology and Oncology, Institute for Cell and Molecular Pathology, Hannover Medical School, Germany; the Institute of Human Genetics, University of Heidelberg, Germany; the Center for Molecular Biology in Medicine, Veterans Affairs, Palo Alto Health Care System, Stanford University School of Medicine, CA; and the Department of Oncology, University Children's Hospital Zurich, Switzerland. Treatment resistance, as indicated by the presence of high levels of minimal residual disease (MRD) after induction therapy and induction consolidation, is associated with a poor prognosis in childhood acute lymphoblastic leukemia (ALL). We hypothesized that treatment resistance is an intrinsic feature of ALL cells reflected in the gene expression pattern and that resistance to chemotherapy can be predicted before treatment. To test these hypotheses, gene expression signatures of ALL samples with high MRD load were compared with those of samples without measurable MRD during treatment. We identified 54 genes that clearly distinguished resistant from sensitive ALL samples. Genes with low expression in resistant samples were predominantly associated with cell-cycle progression and apoptosis, suggesting that impaired cell proliferation and apoptosis are involved in treatment resistance. Prediction analysis using randomly selected samples as a training set and the remaining samples as a test set revealed an accuracy of 84%. We conclude that resistance to chemotherapy seems at least in part to be an intrinsic feature of ALL cells. Because treatment response could be predicted with high accuracy, gene expression profiling could become a clinically relevant tool for treatment stratification in the early course of childhood ALL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Schrappe Risk-adapted stratification and treatment of childhood acute lymphoblastic leukaemia Radiat Prot Dosimetry, December 1, 2008; 132(2): 130 - 133. [Abstract] [Full Text] [PDF] C. Flotho, E. Coustan-Smith, D. Pei, C. Cheng, G. Song, C.-H. Pui, J. R. Downing, and D. 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