Natural killer (NK)/
T cell lymphoma usually shows a highly aggressive
clinical course and the overall prognosis is poor. At present, there are no standard therapeutic regimens for this disease. Although chemotherapeutic protocols containing L-
asparaginase (L-Asp) or
pegaspargase (PEG‑Asp) have improved the efficacy of treatment, some patients are resistant to L-Asp or PEG-Asp. Previous studies demonstrated that the elevated expression of
asparagine synthetase (ASNS) is correlated with the resistance to L-Asp or PEG-Asp and may also affect the prognosis in some types of
tumors, but the expression level and clinical significance of ASNS in NK/
T cell lymphoma remain unknown. Therefore, we investigated the expression and clinical significance of ASNS in
lymphoma cell lines and patients with NK/
T cell lymphoma. Firstly, we detected PEG-Asp and L-Asp activity using MTT assay and expression of ASNS using real-time PCR in the 7
lymphoma cell lines. Secondly, we used branched
DNA-liquidchip technology (bDNA-LCT) for detecting ASNS
mRNA in
formalin-fixed,
paraffin-embedded tissue sections in 50 cases of NK/
T cell lymphoma and in 12 cases of
nasal polyps and chronic
rhinitis. Moreover, we analyzed the correlations between the expression of ASNS and the sensitivity to L-Asp and PEG-Asp in 7
lymphoma cell lines and with clinicopathological features and prognosis of NK/
T cell lymphoma patients who used
chemotherapy containing L-Asp and PEG-Asp. There was a marked difference in the sensitivity to L-Asp and PEG-Asp of the 7
lymphoma cell lines. YTS and SNK-6 cells were highly sensitive to PEG-Asp and had relatively low levels of ASNS
mRNA expression. Hut-78, Jurkat and Karpas 299 cells were naturally resistant to PEG-Asp, and the ASNS expression levels were extremely high. The expression level of ASNS was relatively low in the NK/
T cell lymphoma tissue compared to levels in the
nasal polyps and chronic
rhinitis (0.480±0.307 vs. 0.739±0.267; P=0.009). ASNS expression level was associated with III-IV
tumor stage (P=0.041) and a high International Prognostic Index (P=0.018) in patients with NK/
T cell lymphoma. The NK/
T cell lymphoma patients with higher ASNS expression had a reduced median survival time when compared with the survival of patients with low ASNS expression (P=0.033). Cox regression test showed that the ASNS expression level is an independent prognostic factor for NK/
T cell lymphoma patients. In conclusion, the expression of ASNS was closely related with the sensitivity of
lymphoma cell lines to L-Asp and PEG-Asp in vitro and also had a certain effect on the survival of NK/
T cell lymphoma patients. In conclusion, high ASNS expression in NK/
T cell lymphoma is correlated with worse clinicopathological features.