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

Wen-jian Liu,1,2,* Hua Wang,1,2,* Xiong-wen Peng,1,2,* Wei-da Wang,1,2 Na-wei Liu,1,2 Yang Wang,1,2 Yue Lu1,2 1Laboratory of Hematology Oncologytate, Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, People’s Republic of China; 2Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China *These authors contributed equally to this work Background: Although asparagine synthetase (AsnS) is associated with drug resistance in leukemia, its function in extranodal natural killer (NK)/T-cell lymphoma (ENKTL) remains unclear. Methods: 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. Results: 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 IC50 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. Conclusion: 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. Keywords: asparagine synthetase, extranodal natural killer/T-cell lymphomax, asparaginase resistanc