SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on November 14, 2002; DOI 10.1182/blood-2002-08-2446. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-08-2446v1 101/7/2743    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 Stams, W. A. G. Articles by Pieters, R. Search for Related Content PubMed PubMed Citation Articles by Stams, W. A. G. Articles by Pieters, R. Related Collections Neoplasia Oncogenes and Tumor Suppressors Gene Expression Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 April 2003, Vol. 101, No. 7, pp. 2743-2747 NEOPLASIA Sensitivity to L-asparaginase is not associated with expression levels of asparagine synthetase in t(12;21)+ pediatric ALL Wendy A. G. Stams, Monique L. den Boer, H. Berna Beverloo, Jules P. P. Meijerink, Rolinda L. Stigter, Elisabeth R. van Wering, Gritta E. Janka-Schaub, Rosalyn Slater, and Rob Pieters From the Erasmus MC/University Medical Center Rotterdam/Sophia Children's Hospital, Division of Pediatric Oncology/Hematology, Rotterdam, the Netherlands; Erasmus MC/University Medical Center Rotterdam, Department of Clinical Genetics, Rotterdam, the Netherlands; Dutch Childhood Leukemia Study Group, The Hague, the Netherlands; Cooperative ALL (COALL) Study Group, Hamburg, Germany; and Erasmus MC/University Medical Center Rotterdam, Department of Cell Biology and Genetics, Rotterdam, the Netherlands. The (12;21) translocation resulting in TEL/AML1 gene fusion is present in about 25% of childhood precursor B-lineage acute lymphoblastic leukemia (ALL) and is associated with a good prognosis and a high cellular sensitivity to L-asparaginase (L-Asp). ALL cells are thought to be sensitive to L-Asp due to lower asparagine synthetase (AS) levels. Resistance to L-Asp may be caused by an elevated cellular level of AS or by the ability of resistant cells to rapidly induce the expression of the AS gene on L-Asp exposure. AS may be a target regulated by t(12;21). We studied the relationship between t(12;21) and the mRNA level of AS to investigate a possible mechanism underlying L-Asp sensitivity. Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis surprisingly revealed that 30 patients positive for t(12;21) expressed 5-fold more AS mRNA compared with 17 patients negative for t(12;21) (P = .008) and 11 samples from healthy controls (P = .016). The mRNA levels of AS between t(12;21) ALL and healthy controls did not differ. No difference was found between ALL patients positive or negative for t(12;21) in the capacity to up-regulate AS after in vitro L-Asp exposure, excluding a defective capacity for t(12;21) cells in up-regulating AS on L-Asp exposure. Moreover, no correlation was observed between AS mRNA expression and sensitivity to L-Asp. We conclude that the sensitivity of t(12;21)+ childhood ALL to L-Asp is not associated with the expression level of the AS gene. Furthermore, we contradict the general thought that leukemic cells specifically lack AS compared with normal bone marrow and blood cells. © 2003 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: P. L. Lorenzi, J. Llamas, M. Gunsior, L. Ozbun, W. C. Reinhold, S. Varma, H. Ji, H. Kim, A. A. Hutchinson, E. C. Kohn, et al. Asparagine synthetase is a predictive biomarker of L-asparaginase activity in ovarian cancer cell lines Mol. Cancer Ther., October 1, 2008; 7(10): 3123 - 3128. [Abstract] [Full Text] [PDF] P. L. Lorenzi, W. C. Reinhold, M. Rudelius, M. Gunsior, U. Shankavaram, K. J. Bussey, U. Scherf, G. S. Eichler, S. E. Martin, K. Chin, et al. Asparagine synthetase as a causal, predictive biomarker for L-asparaginase activity in ovarian cancer cells Mol. Cancer Ther., November 1, 2006; 5(11): 2613 - 2623. [Abstract] [Full Text] [PDF] R. B. Reinert, L. M. Oberle, S. A. Wek, P. Bunpo, X. P. Wang, I. Mileva, L. O. Goodwin, C. J. Aldrich, D. L. Durden, M. A. McNurlan, et al. Role of Glutamine Depletion in Directing Tissue-specific Nutrient Stress Responses to L-Asparaginase J. Biol. Chem., October 20, 2006; 281(42): 31222 - 31233. [Abstract] [Full Text] [PDF] A. Holleman, M. L. den Boer, M. H. Cheok, K. M. Kazemier, D. Pei, J. R. Downing, G. E. Janka-Schaub, U. Gobel, U. B. Graubner, C.-H. Pui, et al. Expression of the outcome predictor in acute leukemia 1 (OPAL1) gene is not an independent prognostic factor in patients treated according to COALL or St Jude protocols Blood, September 15, 2006; 108(6): 1984 - 1990. [Abstract] [Full Text] [PDF] M. L. Loh, M. A. Goldwasser, L. B. Silverman, W.-M. Poon, S. Vattikuti, A. Cardoso, D. S. Neuberg, K. M. Shannon, S. E. Sallan, and D. G. Gilliland Prospective analysis of TEL/AML1-positive patients treated on Dana-Farber Cancer Institute Consortium Protocol 95-01 Blood, June 1, 2006; 107(11): 4508 - 4513. [Abstract] [Full Text] [PDF] I. M. Appel, M. L. den Boer, J. P. P. Meijerink, A. J. P. Veerman, N. C. M. Reniers, and R. Pieters Up-regulation of asparagine synthetase expression is not linked to the clinical response L-asparaginase in pediatric acute lymphoblastic leukemia Blood, June 1, 2006; 107(11): 4244 - 4249. [Abstract] [Full Text] [PDF] A. Holleman, M. L. den Boer, R. X. de Menezes, M. H. Cheok, C. Cheng, K. M. Kazemier, G. E. Janka-Schaub, U. Gobel, U. B. Graubner, W. E. Evans, et al. The expression of 70 apoptosis genes in relation to lineage, genetic subtype, cellular drug resistance, and outcome in childhood acute lymphoblastic leukemia Blood, January 15, 2006; 107(2): 769 - 776. [Abstract] [Full Text] [PDF] W. A. G. Stams, M. L. den Boer, A. Holleman, I. M. Appel, H. B. Beverloo, E. R. van Wering, G. E. Janka-Schaub, W. E. Evans, and R. Pieters Asparagine synthetase expression is linked with L-asparaginase resistance in TEL-AML1-negative but not TEL-AML1-positive pediatric acute lymphoblastic leukemia Blood, June 1, 2005; 105(11): 4223 - 4225. [Abstract] [Full Text] [PDF] W. A.G. Stams, M. L. den Boer, H. B. Beverloo, J. P.P. Meijerink, E. R. van Wering, G. E. Janka-Schaub, and R. Pieters Expression Levels of TEL, AML1, and the Fusion Products TEL-AML1 and AML1-TEL versus Drug Sensitivity and Clinical Outcome in t(12;21)-Positive Pediatric Acute Lymphoblastic Leukemia Clin. Cancer Res., April 15, 2005; 11(8): 2974 - 2980. [Abstract] [Full Text] [PDF] B. M. Fine, G. J.L. Kaspers, M. Ho, A. H. Loonen, and L. M. Boxer A Genome-Wide View of the In vitro Response to L-Asparaginase in Acute Lymphoblastic Leukemia Cancer Res., January 1, 2005; 65(1): 291 - 299. [Abstract] [Full Text] [PDF] C.-H. Pui, M. V. Relling, and J. R. Downing Acute Lymphoblastic Leukemia N. Engl. J. Med., April 8, 2004; 350(15): 1535 - 1548. [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020