Ikaros和FUT4在儿童急性淋巴细胞白血病中的表达及其相关性研究  

Expre ssion of Ikaros and FUT4 in Children's Acute Lymphoblastic Leukemia and Their Relationship

作　　者：易丽君 李红[2] 郭智彬[2] 刘志强[2] 周菁[2] 吴崇军[2] 曾小平 YI Li-Jun;LI Hong;GUO Zhi-Bing;LIU Zhi-Qiang;ZHOU Jing;WU Chong-Jun;ZENG Xiao-Ping(Medical School of Nanchang University,Nanchang 330006,Jiangxi Province,China;Jiangxi Provincial Children's Hospital,Nanchang 330006,Jiangxi Province,China)

机构地区：[1]南昌大学基础医学院,江西南昌330006 [2]江西省儿童医院(中心实验室),江西南昌330006

出　　处：《中国实验血液学杂志》2019年第1期1-6,共6页Journal of Experimental Hematology

基　　金：国家自然科学基金项目(31500653);江西省科技厅重大项目(20133BBG70023);江西省卫计委科技计划项目(20161121);江西省自然科学基金项目(20171BAB205043)

摘　　要：目的:通过分析临床样本Ikaros功能状态与岩藻糖基转移酶Ⅳ(fucosyltransferaseⅣ,FUT4)表达水平的相关性,探讨Ikaros调控FUT4表达的可能分子机制,为儿童ALL的个性化治疗靶点提供理论依据。方法:采用巢式PCR及克隆测序法鉴定儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL) Ikaros的表达亚型,计算功能型比率;通过荧光定量PCR检测FUT4 mRNA的相对表达水平,以血小板减少性紫癜(idiopathic thrombocytopenic purpura,ITP)患儿的骨髓样本为对照组,利用ΔΔCt法分析初诊未治的ALL患儿FUT4相对表达水平;分析Ikaros的功能状态与FUT4表达的相关性。结果:110例ALL中,功能亚型Ikaros以Ikaros1(Ik1)和Ikaros2(Ik2)为主,无功能亚型以Ikaros6(Ik6)为主,其Ik6的表达率为20. 91%,其中3例患儿单纯表达Ik6(2. 73%);功能型与Ik6杂合表达比例为18. 18%,且在复发患儿中Ik6表达比例升高。初诊ALL的FUT4的表达水平高于对照组,随着治疗缓解其表达降低,复发患儿的FUT4表达升高。通过2者的相关性分析,Ikaros的功能型比例与FUT4呈负相关(r=-0. 6329),而Ik6的表达量与其成正相关(r=0. 6605)。结论:显性负向型Ik6是预后的独立危险因素,与儿童ALL复发密切相关,Ikaros调控FUT4的表达且呈负相关可能是儿童急性淋巴细胞白血病预后的机制之一。Objective: To explore the possible molecular mechanism of Ikaros regulation on FUT4 expression by analyzing the correlation of the functional state of Ikaros w ith level of FUT4 expression,so as to provide the theoretical basis for personalized treatment in children w ith ALL. Methods:The subtypes of Ikaros w ere identified by nested PCR and sequencing. The expression level of FUT4 w as detected by quantitative PCR and analyzed by ΔΔCt method in the early stage of treatment,remission and relapse of ALL. Results: Ik1 and Ik2 w ere the main functional subtypes,and the dominant negative Ikaros w as Ik6;the Ik6 w as detected in 23 patients w ith ALL. It w as found that 2. 73% patients expressing Ik6 alone and 18. 18% patients w ith heterozygous expression w ere detected. The expression of FUT4 in the new ly diagnosed ALL w as higher than that in the control group,and the functional Ikaros negatively correlated w ith the FUT4 expression( r =-0. 6329). Conclusion: Dominant negative Ikaros closely correlated w ith the relapse of acute lymphoblastic leukemia in children. The functional Ikaros negatively correlated w ith FUT4 expression. Ikaros inhibit the transcriptional activity of FUT4,that may be the molecular mechanism of Ikaros regulating the expression of FUT4.

关 键 词：锌指转录因子 IKAROS 显性负向亚型 岩藻糖基转移酶Ⅳ 急性淋巴细胞白血病 

分 类 号：R733.71[医药卫生—肿瘤]