Asparagine synthetase expression is associated with the sensitivity to asparaginase in extranodal natural killer/T-cell lymphoma in vivo and in vitro

Although asparagine synthetase (AsnS) is associated with drug resistance in leukemia, its function in extranodal natural killer (NK)/T-cell lymphoma (ENKTL) remains unclear. The present study investigated the relationship between baseline AsnS mRNA levels and response to asparaginase in ENKTL cell l...

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Bibliographic Details
Published in:OncoTargets and therapy 2018-01, Vol.11, p.6605-6615
Main Authors: Liu, Wen-Jian, Wang, Hua, Peng, Xiong-Wen, Wang, Wei-da, Liu, Na-Wei, Wang, Yang, Lu, Yue
Format: Article
Language:English
Subjects:
Analysis
Asparagine
Cancer therapies
Cell cycle
Drug resistance
Enzymes
Glycoproteins
Health aspects
Leukemia
Ligases
Lymphoma
Medical prognosis
Non-Hodgkin's lymphomas
Original Research
Pediatrics
Penicillin
Polymerase chain reaction
Prostate
Proteins
RNA
T cells
T-cell lymphoma
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Summary:Although asparagine synthetase (AsnS) is associated with drug resistance in leukemia, its function in extranodal natural killer (NK)/T-cell lymphoma (ENKTL) remains unclear. The present study investigated the relationship between baseline AsnS mRNA levels and response to asparaginase in ENKTL cell lines. It also determined whether upregulating or downregulating the AsnS mRNA level induces or reverses asparaginase-resistant phenotype. Interestingly, considerable differences were observed in the sensitivity to asparaginase of the five ENKTL cell lines. The AsnS expression levels were positively correlated with the IC values. In addition, the asparaginase resistance was induced or reversed by upregulating or downregulating the AsnS mRNA level in vivo and in vitro. Functional analyses indicated that AsnS did not affect the proliferation and apoptosis of ENKTL cells in the absence of asparaginase. Together, the data stress the importance of AsnS in the sensitivity to asparaginase in ENKTL and suggest a different therapeutic strategy for patients with a different level of AsnS expression.
ISSN:1178-6930
1178-6930
DOI:10.2147/OTT.S155930