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Blood, 1 June 2005, Vol. 105, No. 11, pp. 4223-4225. Prepublished online as a Blood First Edition Paper on February 17, 2005; DOI 10.1182/blood-2004-10-3892. This Article Full Text (PDF) All Versions of this Article: 2004-10-3892v1 105/11/4223    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 Articles by Pieters, R. Search for Related Content PubMed PubMed Citation Articles by Stams, W. A Articles by Pieters, R. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 7, 2004 Accepted January 14, 2005 Asparagine synthetase expression is linked with L-asparaginase resistance in TEL-AML1 negative, but not in TEL-AML1 positive pediatric acute lymphoblastic leukemia Wendy A Stams, Monique L den Boer*, Amy Holleman, Inge M Appel, H B Beverloo, Elisabeth R van Wering, Gritta E Janka-Schaub, William E Evans, 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 Oncology Group, The Hague, The Netherlands COALL study group, Hamburg, Germany Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA Division of Pediatric Oncology / Hematology, Erasmus MC / University Medical Center Rotterdam / Sophia Children's Hospital, Rotterdam, The Netherlands; Dutch Childhood Oncology Group, The Hague, The Netherlands * Corresponding author; email: m.l.denboer{at}erasmusmc.nl. Resistance to L-Asparaginase in leukemic cells may be caused by an elevated cellular expression of asparagine synthetase (AS). Previously, we reported that high AS expression did not correlate to L-Asparaginase resistance in TEL-AML1 positive B-lineage ALL. In the present study, we confirmed this finding in TEL-AML1 positive patients (n=28) using microarrays. In contrast, 35 L-Asparaginase resistant TEL-AML1 negative B-lineage ALL patients had a significant 3.5-fold higher AS expression than 43 sensitive patients (p=0.0004). Using RTQ-PCR, this finding was confirmed in an independent group of 39 TEL-AML1 negative B-lineage ALL patients (p=0.03). High expression of AS was associated with poor prognosis (4-yrs pDFS 58% ± 11%) compared to low expression (4-yrs pDFS 83% ± 7%; p=0.009). We conclude that resistance to L-Asparaginase and relapse-risk are associated with high expression of AS in TEL-AML1 negative but not in TEL-AML1 positive B-lineage ALL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Campana Molecular Determinants of Treatment Response in Acute Lymphoblastic Leukemia Hematology, January 1, 2008; 2008(1): 366 - 373. [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] S. Chiaretti, X. Li, R. Gentleman, A. Vitale, K. S. Wang, F. Mandelli, R. Foa, and J. Ritz Gene Expression Profiles of B-lineage Adult Acute Lymphocytic Leukemia Reveal Genetic Patterns that Identify Lineage Derivation and Distinct Mechanisms of Transformation Clin. Cancer Res., October 15, 2005; 11(20): 7209 - 7219. [Abstract] [Full Text] [PDF]

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