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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 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 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 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. Related Collections Neoplasia Gene Expression Genomics Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Genomewide identification of prednisolone-responsive genes in acute lymphoblastic leukemia cells Wim J. E. Tissing1,2, Monique L. den Boer1, Jules P. P. Meijerink1, Renee X. Menezes1,3, Sigrid Swagemakers4, Peter J. van der Spek4, Stephen E. Sallan5, Scott A. Armstrong5, and Rob Pieters1 1 Department of Pediatric Oncology/Hematology, Erasmus MC/Sophia Children's Hospital, Rotterdam, The Netherlands; 2 Department of Pediatric Oncology/Hematology, Beatrix Children's Hospital, University of Groningen and University Medical Center Groningen, The Netherlands; 3 Center for Human and Clinical Genetics, Leiden University Medical Center, The Netherlands; 4 Department of Bioinformatics, Erasmus MC, Rotterdam, The Netherlands; 5 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 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 on 3 and 8 hours of prednisolone exposure in leukemic cells of 13 children as compared with nonexposed 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 < .001 and false discovery rate < 10%) with 39 genes being up-regulated (median, 2.4-fold) and 12 genes were down-regulated (median, 1.7-fold). Twenty-one of those genes have not been identified before to be transcriptionally regulated by prednisolone. Two of the 3 most highly up-regulated genes were tumor suppressor genes, that is, 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 3 major routes, namely MAPK pathways (9 genes), NF-B signaling (11 genes), and carbohydrate metabolism (5 genes). Biologic 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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