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Prepublished online as a Blood First Edition Paper on November 14, 2002; DOI 10.1182/blood-2002-08-2446. This Article 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 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. Social Bookmarking                   What's this? Submitted August 9, 2002 Accepted October 31, 2002 Sensitivity to L-Asparaginase is not associated with expression levels of asparagine synthetase in t(12;21) positive 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 Division of Pediatric Oncology / Hematology, Erasmus MC / University Medical Center Rotterdam / Sophia Children's Hospital, Rotterdam, The Netherlands Department of Clinical Genetics, Erasmus MC / University Medical Center Rotterdam, Rotterdam, The Netherlands Dutch Childhood Leukemia Study Group, The Hague, The Netherlands COALL Study Group, Hamburg, Germany Department of Cell Biology and Genetics, Erasmus MC / University Medical Center Rotterdam, Rotterdam, The Netherlands * Corresponding author; email: stams{at}kgk.fgg.eur.nl. The (12;21) translocation resulting in TEL/AML1 gene fusion is present in ~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 and/or by the ability of resistant cells to rapidly induce the expression of the AS gene upon 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 in order to investigate a possible mechanism underlying L-Asp sensitivity. Real-time quantitative RT-PCR analysis surprisingly revealed that 30 t(12;21) positive patients expressed 5-fold more AS mRNA compared to 17 t(12;21) negative patients (p=0.008) and 11 samples of healthy controls (p=0.016). The mRNA levels of AS between t(12;21) negative ALL and healthy controls did not differ. No difference was found between t(12;21) positive and negative ALL patients in the capacity to upregulateAS after in vitro L-Asp exposure, excluding a defective capacity for t(12;21) cells in upregulating AS upon L-Asp exposure. Moreover, no correlation was observed betweenAS mRNA expression and sensitivity to L-Asp. We conclude that the sensitivity of t(12;21) positive 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 to normal bone marrow and blood cells. 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. 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