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Blood, 1 May 2007, Vol. 109, No. 9, pp. 3929-3935. Prepublished online as a Blood First Edition Paper on January 11, 2007; DOI 10.1182/blood-2006-11-056366. This Article Full Text (PDF) All Versions of this Article: blood-2006-11-056366v1 109/9/3929    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 Tissing, W. J.E. Articles by Pieters, R. Search for Related Content PubMed PubMed Citation Articles by Tissing, W. J.E. Articles by Pieters, R. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 7, 2006 Accepted December 21, 2006 Genome-wide identification of prednisolone-responsive genes in acute lymphoblastic leukemia cells Wim J.E. Tissing, Monique L. Den Boer*, Jules P.P. Meijerink, Renee X. Menezes, Sigrid Swagemakers, Peter J. van der Spek, Stephen E. Sallan, Scott A. Armstrong, and Rob Pieters Dept of Pediatric Oncology/Hematology, University Medical Centre Groningen, Beatrix Childrens Hospital, University of Groningen, Groningen, Netherlands Dept of Pediatric Oncology/Hematology, Erasmus MC / Sophia Children's Hospital, Rotterdam, Netherlands Center for Human & Clinical Genetics, Leiden University Medical Center, Leiden, Netherlands Dept of Bioinformatics, Erasmus MC, Rotterdam, Netherlands Dept of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States * Corresponding author; email: m.l.denboer{at}erasmusmc.nl. Glucocorticoids are keystone drugs in the treatment of childhood acute lymphoblastic leukemia (ALL). To get more insight in signal transduction pathways involved in glucocorticoid-induced apoptosis, Affymetrix U133A GeneChips were used to identify transcriptionally regulated genes upon 3 and 8 hours of prednisolone exposure in leukemic cells of 13 children as compared to non-exposed cells. Following 3 hours of exposure no significant changes in gene expression could be identified. Following 8 hours of exposure, 51 genes were differentially expressed (p < 0.0005 and false discovery rate < 10%) with 39 genes being upregulated (median 2.4-fold) and 12 genes downregulated (median 1.7-fold). Twenty-one of those genes have not been identified before to be transcriptionally regulated by prednisolone. Two of the three most highly upregulated genes were tumor suppressor genes, i.e. Thioredoxin interacting protein (TXNIP, 3.7-fold) and zinc finger and BTB domain containing 16 (ZBTB16, 8.8-fold). About 50% of the differentially expressed genes were functionally categorized in three major routes, namely MAPK pathways (9 genes), NF-B signaling (11 genes) and carbohydrate metabolism (5 genes). Biological characterization of these genes and pathways might elucidate the action of glucocorticoids in ALL cells, possibly suggesting causes of glucocorticoid resistance and new potential targets for therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. J. Yang, C. Cheng, W. Yang, D. Pei, X. Cao, Y. Fan, S. B. Pounds, G. Neale, L. R. Trevino, D. French, et al. Genome-wide Interrogation of Germline Genetic Variation Associated With Treatment Response in Childhood Acute Lymphoblastic Leukemia JAMA, January 28, 2009; 301(4): 393 - 403. [Abstract] [Full Text] [PDF] A. Manabe, A. Ohara, D. Hasegawa, K. Koh, T. Saito, N. Kiyokawa, A. Kikuchi, H. Takahashi, K. Ikuta, Y. Hayashi, et al. Significance of the complete clearance of peripheral blasts after 7 days of prednisolone treatment in children with acute lymphoblastic leukemia: the Tokyo Children's Cancer Study Group Study L99-15 Haematologica, August 1, 2008; 93(8): 1155 - 1160. [Abstract] [Full Text] [PDF] M. C. Davis, K. S. McColl, F. Zhong, Z. Wang, M. H. Malone, and C. W. Distelhorst Dexamethasone-induced Inositol 1,4,5-Trisphosphate Receptor Elevation in Murine Lymphoma Cells Is Not Required for Dexamethasone-mediated Calcium Elevation and Apoptosis J. Biol. Chem., April 18, 2008; 283(16): 10357 - 10365. [Abstract] [Full Text] [PDF] R. A. Davis Searching for Causality of Knocking Out Txnip: Is Txnip Missing in Action? Circ. Res., December 7, 2007; 101(12): 1216 - 1218. [Full Text] [PDF] E. Laane, T. Panaretakis, K. Pokrovskaja, E. Buentke, M. Corcoran, S. Soderhall, M. Heyman, J. Mazur, B. Zhivotovsky, A. Porwit, et al. Dexamethasone-induced apoptosis in acute lymphoblastic leukemia involves differential regulation of Bcl-2 family members Haematologica, November 1, 2007; 92(11): 1460 - 1469. [Abstract] [Full Text] [PDF]

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