hnRNPK/Beclin1信号异常对Ph^(+)白血病伊马替尼耐药的影响  

The Effect of hnRNPK/Beclin1 Signaling on the Drug Resistance of Imatinib in Ph^(+)Leukemia

作　　者：张进芳[1] 刘晓力[2] 宗飒[1] ZHANG Jin-Fang;LIU Xiao-Li;ZONG Sa(Department of Paediatric Hematology,Guangdong Provincial People’s Hospital,Guangdong Academy of Medical Sciences,Guangzhou 510080,Guangdong Province,China;Department of Hematology,Nanfang Hospital,Southern Medical University,Guangzhou 510515,Guangdong Province,China)

机构地区：[1]广东省医学科学院,广东省人民医院儿童血液科,广东广州510080 [2]南方医科大学附属南方医院血液科,广东广州510515

出　　处：《中国实验血液学杂志》2022年第3期750-754,共5页Journal of Experimental Hematology

基　　金：广东省基础与应用基础研究基金(No.2018A030313524)。

摘　　要：目的:探索hnRNPK/Beclin1信号异常与Ph^(+)白血病伊马替尼耐药的相关性。方法:用WB法检测hnRNPK在伊马替尼敏感和耐药细胞株中的表达水平差异。RNAi法沉默hnRNPK在耐药株中的表达水平。在hnRNPK表达调变前后,分别使用CCK-8法检测耐药细胞株对伊马替尼药物敏感性的变化,以及使用WB法检测自噬蛋白LC3Ⅰ/Ⅱ及Beclin1的表达水平变化。结果:hnRNPK在伊马替尼耐药细胞株中的表达水平较敏感株明显增高,使用RNAi法降低hnRNPK的表达水平后,耐药株对伊马替尼的敏感性可以部分恢复,且自噬相关蛋白LC3Ⅰ/Ⅱ及Beclin1的表达与hnRNPK的表达变化一致。结论:hnRNPK/Beclin1信号异常调控细胞自噬,进而参与Ph^(+)白血病伊马替尼耐药。Objective:To explore the effect of hnRNPK/Beclin1 signaling on the drug resistance of imatinib in Ph^(+)l eukemia.Methods:Expression level of hnRNPK was verified in the imatinib resistant and sensitive Ph^(+)leukemia cell lines by using Western blot.hnRNPK expression was down-regulated by using RNAi.Expression level of LC3Ⅰ/Ⅱand B eclin1 were detected by Western blot and the sensitivity of imatinib was analyzed by CCK-8 assay before and after m odulation of hnRNPK expression.Results:hnRNPK showed overexpressed in imatinib resistant leukemia cell line.After the expression level of hnRNPK was down-regulated by RNAi,the sensitivity of drug resistance lines to imatinib restored,while the expression level of LC3Ⅰ/Ⅱand Beclin1 were consistant with the modulation of hnRNPK expression.C onclusion:hnRNP K/Beclin1 signaling may be involved in the development of imatinib resistance in Ph^(+)leukemia t hrough the regulation of autophagy.

关 键 词：hnRNP K BECLIN1 细胞自噬 白血病 伊马替尼 耐药 

分 类 号：R733.7[医药卫生—肿瘤]