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Blood, 1 June 2006, Vol. 107, No. 11, pp. 4244-4249. Prepublished online as a Blood First Edition Paper on February 23, 2006; DOI 10.1182/blood-2005-06-2597. This Article Full Text (PDF) All Versions of this Article: 2005-06-2597v1 107/11/4244    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 Appel, I. M Articles by Pieters, R. Search for Related Content PubMed PubMed Citation Articles by Appel, I. M Articles by Pieters, R. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 6, 2005 Accepted December 10, 2005 Upregulation of asparagine synthetase expression is not linked to the clinical response to L-asparaginase in pediatric acute lymphoblastic leukemia Inge M Appel, Monique L den Boer*, Jules P Meijerink, Anjo J Veerman, Nathalie C Reniers, and Rob Pieters Department of Pediatric Oncology/Hematology, Erasmus MC/ Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam, The Netherlands Dutch Childhood Oncology Group, The Hague, The Netherlands * Corresponding author; email: m.l.denboer{at}erasmusmc.nl. L-Asparaginase is an effective drug for treatment of children with acute lymphoblastic leukemia. The effectiveness is generally thought to result from a rapid depletion of asparagine in serum and cells. Asparagine synthetase (AS) opposes the action of L-Asp by re-synthesis of asparagine. In vitro, resistance to L-Asp has been associated with upregulation of AS mRNA expression. We monitored AS mRNA levels in leukemic cells before and during 5 days after 1000 IU/m2 i.v. of pegylated L-asparaginase (PEG-Asp) in a therapeutic window in children with ALL at initial diagnosis. Within 24 hours AS mRNA levels increased by 3.5 fold and remained stable in the following four days. Baseline and L-Asp-induced expression levels of AS did not differ between clinically good, intermediate and poor responders to PEG-Asp. No significant difference of AS mRNA upregulation was found between precursor B and T-ALL, nor between hyperdiploids, TEL/AML1 rearranged ALL or absence of genetic abnormalities. In 3 out of 12 T-ALL patients even a slight downregulation of ASmRNA expression upon L-Asp exposure was found. Concluding, although L-Asp exposure induces the expression of AS mRNA, the upregulated gene expression does not correlate with an early clinical poor response to this drug in children with ALL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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]

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