SEARCH:   Advanced

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 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 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 Brief Reports Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Brief report Asparagine synthetase expression is linked with L-asparaginase resistance in TEL-AML1–negative but not TEL-AML1–positive pediatric acute lymphoblastic leukemia Wendy A. G. Stams, Monique L. den Boer, Amy Holleman, Inge M. Appel, H. Berna Beverloo, Elisabeth R. van Wering, Gritta E. Janka-Schaub, William E. Evans, and Rob Pieters From the Erasmus Medical Center (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 Oncology Group, The Hague, The Netherlands; Cooperative Acute Lymphoblastic Leukemia (COALL) Study Group, Hamburg, Germany; and St Jude Children's Research Hospital, Department of Pharmaceutical Sciences, Memphis, TN. 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 acute lymphoblastic leukemia (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 < .001). Using real-time quantitative polymerase chain reaction (RTQ-PCR), this finding was confirmed in an independent group of 39 TEL-AML1–negative B-lineage ALL patients (P = .03). High expression of AS was associated with poor prognosis (4-year probability of disease-free survival [pDFS] 58% ± 11%) compared with low expression (4-year pDFS 83% ± 7%; P = .009). We conclude that resistance to L-asparaginase and relapse risk are associated with high expression of AS in TEL-AML1–negative but not 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: 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]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020