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Blood, 15 July 2006, Vol. 108, No. 2, pp. 711-717. Prepublished online as a Blood First Edition Paper on March 28, 2006; DOI 10.1182/blood-2006-02-002824. This Article Full Text Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: blood-2006-02-002824v1 108/2/711    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 Bhojwani, D. Articles by Carroll, W. L. Search for Related Content PubMed PubMed Citation Articles by Bhojwani, D. Articles by Carroll, W. L. Related Collections Apoptosis Cell Cycle Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Biologic pathways associated with relapse in childhood acute lymphoblastic leukemia: a Children's Oncology Group study Deepa Bhojwani, Huining Kang, Naomi P. Moskowitz, Dong-Joon Min, Hokyung Lee, Jeffrey W. Potter, George Davidson, Cheryl L. Willman, Michael J. Borowitz, Ilana Belitskaya-Levy, Stephen P. Hunger, Elizabeth A. Raetz, and William L. Carroll From the New York University (NYU) Cancer Institute and Division of Pediatric Hematology/Oncology, New York, NY; Department of Biostatistics, NYU School of Medicine, New York, NY; Department of Pediatrics, Mount Sinai School of Medicine, New York, NY; The Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM; Sandia National Laboratories, Albuquerque, NM; Department of Pediatrics, University of Florida College of Medicine and the University of Florida Shands Cancer Center, Gainesville, FL; and the Department of Pathology and Oncology, Johns Hopkins Medical Institutions, Baltimore, MD. Outcome for children with childhood acute lymphoblastic leukemia (ALL) who relapse is poor. To gain insight into the mechanisms of relapse, we analyzed gene-expression profiles in 35 matched diagnosis/relapse pairs as well as 60 uniformly treated children at relapse using the Affymetrix platform. Matched-pair analyses revealed significant differences in the expression of genes involved in cell-cycle regulation, DNA repair, and apoptosis between diagnostic and early-relapse samples. Many of these pathways have been implicated in tumorigenesis previously and are attractive targets for intervention strategies. In contrast, no common pattern of changes was observed among late-relapse pairs. Early-relapse samples were more likely to be similar to their respective diagnostic sample while we noted greater divergence in gene-expression patterns among late-relapse pairs. Comparison of expression profiles of early- versus late-relapse samples indicated that early-relapse clones were characterized by overexpression of biologic pathways associated with cell-cycle regulation. These results suggest that early-relapse results from the emergence of a related clone, characterized by the up-regulation of genes mediating cell proliferation. In contrast, late relapse appears to be mediated by diverse pathways. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Marston, V. Weston, J. Jesson, E. Maina, C. McConville, A. Agathanggelou, A. Skowronska, K. Mapp, K. Sameith, J. E. Powell, et al. Stratification of pediatric ALL by in vitro cellular responses to DNA double-strand breaks provides insight into the molecular mechanisms underlying clinical response Blood, January 1, 2009; 113(1): 117 - 126. [Abstract] [Full Text] [PDF] D. Bhojwani, J. Wang, J. J Yang, D. Morrison, M. Devidas, E. Raetz, S. P. Hunger, M. V. Relling, and W. L. Carroll Evolution of Gene Expression Signatures in Relapsed Childhood Acute Lymphoblastic Leukemia Differs Based on Timing of Relapse. Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 3345 - 3345. [Abstract] M. J. Borowitz, M. Devidas, S. P. Hunger, W. P. Bowman, A. J. Carroll, W. L. Carroll, S. Linda, P. L. Martin, D. J. Pullen, D. Viswanatha, et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children's Oncology Group study Blood, June 15, 2008; 111(12): 5477 - 5485. [Abstract] [Full Text] [PDF] C. Flotho, E. Coustan-Smith, D. Pei, C. Cheng, G. Song, C.-H. Pui, J. R. Downing, and D. Campana A set of genes that regulate cell proliferation predicts treatment outcome in childhood acute lymphoblastic leukemia Blood, August 15, 2007; 110(4): 1271 - 1277. [Abstract] [Full Text] [PDF]

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