Relationship between the antileukemic activity of L-asparaginase and Asn level around leukemic cells
LI Ben-Shang, LUO Chang-Ying, HE Ying-Yi, JIANG Hua, GU Long-Jun
Department of Hematology/ Oncology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China. Email: ljguscmc@hotmail.com
Abstract OBJECTIVE: To study the antileukemic activity of L-asparaginase through determining the changes of 4 kinds of amino acids (Asn, Aspa, Glu and Gln) in cell culture medium. METHODS: Following L-Asp treatment with designed concentrations and duration, the IC50 (inhibitory concentration 50%) of 8 kinds of common leukemia cell lines (U937, HL-60, Jurkat, NB4, THP-1, Namalwa, Karpass299, K562) were determined by CCK-8 assay. The changes of the 4 kinds of amino acids mentioned above were detected by high performance liquid chromatography (HPLC). RESULTS: The asparagines in cell culture medium were rapidly exhausted when treated with 0.01 U/mL L-Asp for 4 hrs or 1 U/mL L-Asp for 5 minutes. There were significant differences in the sensitivities to L-Asp of different leukemia cell lines. The sensitivities to L-Asp of various cell lines were dose-dependent. Low concentration of L-Asp resulted in a low IC50 and the IC50 increased following the L-Asp concentration increased. CONCLUSIONS: Different leukemia cell lines have different sensitivities to L-Asp, suggesting that exhaustion of asparagines around leukemia cells could not reflect the treatment efficacy of L-Asp. L-Asp antileukemic activity is dose-dependent, which suggests the importance of high-dose L-Asp on childhood acute lymphoblastic leukemia. ［Chin J Contemp Pediatr, 2010, 12 (7):557-562］
LI Ben-Shang,LUO Chang-Ying,HE Ying-Yi et al. Relationship between the antileukemic activity of L-asparaginase and Asn level around leukemic cells[J]. 中国当代儿科杂志, 2010, 12(07): 557-562.
LI Ben-Shang,LUO Chang-Ying,HE Ying-Yi et al. Relationship between the antileukemic activity of L-asparaginase and Asn level around leukemic cells[J]. CJCP, 2010, 12(07): 557-562.
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