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TLR9激动剂对不同TLR9单核苷酸多态B-ALL的作用

Effect of TLR9 agonists on B-ALL of different TLR9 single nucleotide polymorphisms
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摘要 [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 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),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rs187084或rs5743836/rs187084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)。 [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/rs187084 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.
作者 杜立坤 刘影 胡灵丹 杜志强 崔菁 DU Likun;LIU Ying;HU Lingdan;DU Zhiqiang;CUI Jing(Department of Hematology,The Second People's Hospital of Hengshui,Hengshui 053000;Department of Pathology,The Second People's Hospital of Hengshui,Hengshui 053000;Molecular Laboratory,The Second People's Hospital of Hengshui,Hengshui 053000,China)
出处 《生物技术》 CAS 2024年第6期774-779,共6页 Biotechnology
基金 衡水市科技计划项目(2022014048Z)。
关键词 急性B淋巴细胞白血病 TLR9 单核苷酸多态 TLR9激动剂 P38 P53 BAX IGM acute B lymphocytic leukemia TLR9 single nucleotide polymorphism TLR9 agonist P38 P53 BAX IgM
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