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Asparagine synthetase expression is linked with L-asparaginase resistance in TEL-AML1-negative but not TEL-AML1-positive pediatric acute lymphoblastic leukemia (2005)

Abstract

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.

Publication details

Download	http://hdl.handle.net/1765/8226
Repository	Erasmus University Digital Repository (Netherlands)
Keywords	Asparaginase/therapeutic use, Oligonucleotide Array Sequence Analysis, Aspartate-Ammonia Ligase/analysis/genetics, Child, Core Binding Factor Alpha 2 Subunit, Research Support, Non-U.S. Gov't, Disease-Free Survival, Drug Resistance, Neoplasm, Gene Expression Regulation, Neoplastic, Recurrence, Humans, Leukemia, B-Cell, Acute/drug therapy/mortality, Prognosis, Leukemia, Lymphocytic, Acute/drug therapy/*mortality, Oncogene Proteins, Fusion/analysis
Type	Article
Language	Englisch

Cited publications (1)

Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment (2004)