[目的]探讨TLR9激动剂对不同TLR9单核苷酸多态的急性B淋巴细胞白血病(B-ALL)细胞的作用.[方法]纳入2015年1月-2017年1月收治的B-ALL患者166例,采集B-ALL细胞并检测TLR9基因型.TLR9激动剂CpG 685处理后,检测TLR9不同单核苷酸多态的B-ALL细胞的增殖水平、凋亡水平、共刺激分子(CD40、CD80、CD86和MHC-I)水平、TLR9下游P38/P53/BAX通路关键分子的蛋白水平和IgM分泌水平.[结果]相比于TLR9 WT,TLR9激动剂CpG 685处理后TLR9 rs5743836或rs187084或rs5743836/rs187084的B-ALL细胞具有更低的细胞增殖水平、更高的细胞凋亡水平、更高的共刺激分子水平(1.63±0.20 vs0.82±0.21;1.64±0.28 vs 2.67±0.20;1.00±0.04 vs 3.94±0.29,P＜0.05),并且TLR9下游P38/P53/BAX通路关键分子具有更高的蛋白表达水平,同时具有更高的 IgM 的水平(12.40±2.89 vs 16.75±3.25,P＜0.05)、更高的抗体反应关键因子 AID(0.05±0.01 vs 0.09±0.01,P＜0.05)和 Blimp-1 水平(0.62±0.05 vs 0.83±0.08,P＜0.05).[结论]TLR9 激动剂对 TLR9 rs5743836 或rs1 87084 或 rs5743836/rs1 87084 的 B-ALL 细胞具有更强的促凋亡(1.64±0.28 vs 2.67±0.20)和 IgM 分泌效果(12.40±2.89 vs 16.75±3.25).
Effect of TLR9 agonists on B-ALL of different TLR9 single nucleotide polymorphisms
[Objective]To investigate the effects of TLR9 agonists on acute B lymphoblastic leukemia(B-ALL)cells with dif-ferent TLR9 mononucleotide polymorphisms.[Method]One hundred and sixty-six B-ALL patients admitted to our hospital from January 2015 to January 2017 were included,and B-ALL cells from subjects were collected and tested for TLR9 geno-type.After treatment with TLR9 agonist CpG 685,B-ALL cells with different single nucleotide polymorphisms of TLR9 were examined for proliferation levels,apoptosis levels,co-stimulatory molecules(CD40,CD80,CD86 and MHC-I)levels,protein levels of key molecules of the P38/P53/BAX pathway downstream of TLR9,and IgM secretion levels.[Result]Compared to TLR9 WT,B-ALL cells of TLR9 rs5743836 or rs187084 or rs5743836/rsl87084 treated with TLR9 agonist CpG 685 had low-er levels of cell proliferation,higher levels of apoptosis,and higher levels of co-stimulatory molecules(1.63±0.20 vs 0.82±0.21;1.64±0.28 vs 2.67±0.20;1.00±0.04 vs 3.94±0.29,P＜0.05),and the key molecules of P38/P53/BAX pathway downstream of TLR9 had a higher protein expression level,and a higher IgM level(12.40±2.89 vs 16.75±3.25,12.40±2.89 vs 16.75±3.25,respectively),P＜0.05),higher antibody response key factor AID(0.05±0.01 vs 0.09±0.01,P＜0.05)and Blimp-1 levels(0.62±0.05 vs 0.83±0.08,P＜0.05).[Conclusion]TLR9 agonists had stronger pro-apoptotic(1.64±0.28 vs 2.67±0.20)and IgM secretion(12.40±2.89 vs 16.75±3.25)effects on B-ALL cells of TLR9 rs5743836 or rs187084 or rs5743836/rs187084.
acute B lymphocytic leukemiaTLR9single nucleotide polymorphismTLR9 agonistP38P53BAXIgM
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