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, Rob Pieters

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

70 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)4223-5
Aantal pagina's3
TijdschriftBlood
Volume105
Nummer van het tijdschrift11
DOI's
StatusGepubliceerd - 1 jun. 2005
Extern gepubliceerdJa

Vingerafdruk

Duik in de onderzoeksthema's van 'Asparagine synthetase expression is linked with L-asparaginase resistance in TEL-AML1-negative but not TEL-AML1-positive pediatric acute lymphoblastic leukemia'. Samen vormen ze een unieke vingerafdruk.

Citeer dit