急性淋巴细胞白血病患儿血清miR-17、miR-29c的表达及临床意义
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摘要
目的研究急性淋巴细胞白血病(ALL)患儿血清中miR-17、miR-29c表达水平及其与患儿生存率的关系。方法选择2010年9月～2013年2月在笔者医院初诊为ALL并住院治疗的43例患儿作为病例组,同时期体检健康儿童40例作为对照组。采用RT-PCR检测两组儿童血清中miR-17、miR-29c相对表达量,分析病例组血清miR-17、miR-29c表达水平与患儿初诊白细胞(WBC)计数、免疫分型等临床指标及患儿5年无事件生存率、总生存率的关系。结果病例组儿童血清中miR-17相对表达量显著高于对照组(P<0.05),miR-29c相对表达量显著低于对照组(P<0.05);病例组血清中miR-17表达水平与患儿初诊WBC计数、免疫分型有关(P<0.05),miR-29c表达水平与患儿初诊WBC计数、免疫分型及泼尼松诱导敏感度有关(P<0.05);病例组患儿5年无事件生存率51.16%,总生存率72.09%;生存组患儿血清miR-17相对表达量显著低于死亡组患儿(P<0.05),miR-29c相对表达量显著高于死亡组患儿(P<0.05);miR-17高表达组患儿5年无事件生存率、总生存率均显著低于miR-17低表达组患儿;miR-29c高表达组患儿5年无事件生存率、总生存率均显著高于miR-29c低表达组患儿。结论 ALL患儿血清中miR-17表达上调,miR-29c表达下调,与患儿预后不良有关。
Objective To study the expression levels of miR-17 and miR-29c in serum of children with acute lymphoblastic leukemia(ALL)and their relationships with the survival rate of children. Methods Totally 43 cases of children who diagnosed as ALL and hospitalized in our hospital from September 2010 to February 2013 were selected as case group, and 40 healthy children were used as control group at the same time. RT-PCR was used to detect the relative expressions of miR-17 and miR-29c of children in two groups. The relationships between the levels of miR-17 and miR-29c expression in the case group with the clinical indexes of leukocyte(WBC) count and immunophenotype when first diagnosed, and the 5-year event free survival rate and the total survival rate of the children were analyzed. Results The relative expression of miR-17 in serum of children in case group was significantly higher than that in control group(P<0.05). The relative expression of miR-29c was significantly lower than that in the control group(P<0.05). The expression level of miR-17 in serum of case group was related to WBC count and immunophenotype(P<0.05). The miR-29c expression level was correlated with the WBC count, immunophenotype and prednisone induction sensitivity(P<0.05). The 5-year event free survival rate of case group was 51.16%, and overall survival rate was 72.09%. The relative expression level of serum miR-17 in the survival group was significantly lower than that in the death group(P<0.05). The relative expression of miR-29c was significantly higher than that in the death group(P<0.05). The 5-year event free survival rate and overall survival rate of miR-17 high expression group were significantly lower than those of miR-17 low expression group. The 5-year event free survival rate and overall survival rate of miR-29c high expression group were significantly higher than those of miR-29c low expression group. Conclusion Up-regulation of miR-17 expression and down-regulation of miR-29c expression in serum of children with ALL are associated with poor prognosis.
Objective To study the expression levels of miR-17 and miR-29c in serum of children with acute lymphoblastic leukemia(ALL)and their relationships with the survival rate of children. Methods Totally 43 cases of children who diagnosed as ALL and hospitalized in our hospital from September 2010 to February 2013 were selected as case group, and 40 healthy children were used as control group at the same time. RT-PCR was used to detect the relative expressions of miR-17 and miR-29c of children in two groups. The relationships between the levels of miR-17 and miR-29c expression in the case group with the clinical indexes of leukocyte(WBC) count and immunophenotype when first diagnosed, and the 5-year event free survival rate and the total survival rate of the children were analyzed. Results The relative expression of miR-17 in serum of children in case group was significantly higher than that in control group(P<0.05). The relative expression of miR-29c was significantly lower than that in the control group(P<0.05). The expression level of miR-17 in serum of case group was related to WBC count and immunophenotype(P<0.05). The miR-29c expression level was correlated with the WBC count, immunophenotype and prednisone induction sensitivity(P<0.05). The 5-year event free survival rate of case group was 51.16%, and overall survival rate was 72.09%. The relative expression level of serum miR-17 in the survival group was significantly lower than that in the death group(P<0.05). The relative expression of miR-29c was significantly higher than that in the death group(P<0.05). The 5-year event free survival rate and overall survival rate of miR-17 high expression group were significantly lower than those of miR-17 low expression group. The 5-year event free survival rate and overall survival rate of miR-29c high expression group were significantly higher than those of miR-29c low expression group. Conclusion Up-regulation of miR-17 expression and down-regulation of miR-29c expression in serum of children with ALL are associated with poor prognosis.
引文
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10 Sharifi M,Salehi R,Gheisari Y,et al.Inhibition of microRNA miR-92a induces apoptosis and inhibits cell proliferation in human acute promyelocytic leukemia through modulation of p63 expression[J].Mole Biol Rep,2014,41(5):2799-2808
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12 Scherr M,Elder A,Battmer K,et al.Differential expression of miR-17～92 identifies BCL2 as a therapeutic target in BCR-ABL-positive B-lineage acute lymphoblastic leukemia[J].Leukemia,2014,28(3):554-565
13 Mian YA,Zeleznikle NJ.The miR-17～92 cluster contributes to MLL leukemia through the repression of MEIS1 competitor PKNOX1[J].Leuk Res,2016,46:51-60
14 Gong JN,Yu J,Lin HS,et al.The role,mechanism and potentially therapeutic application of microRNA-29 family in acute myeloid leukemia[J].Cell Death Differ,2014,21(1):100-112
2 周翾,周宇晨,骆燕辉,等.儿童急性淋巴细胞白血病复发60例临床分析[J].中华实用儿科临床杂志,2016,31(12):927-931
3 袁冬妹,吴思英,黄素丽,等.血浆miRNA表达与儿童急性淋巴细胞白血病风险的关联研究[J].中华流行病学杂志,2017,38(9):1252-1258
4 Roden C,Lu J.MicroRNAs in control of stem cells in normal and malignant hematopoiesis[J].Curr Stem Cell Rep,2016,2(3):183-196
5 段瑞.WHO造血与淋巴组织肿瘤分类(2016)[J].诊断病理学杂志,2017,24(12):956-958
6 Nebbioso A,Benedetti R,Conte M,et al.Genetic mutations in epigenetic modifiers as therapeutic targets in acute myeloid leukemia[J].Expert Opin Ther Targets,2015,19(9):1187-1202
7 张珏,张艳丽,李欣,等.CCLG-ALL-2008方案治疗169例儿童急性淋巴细胞白血病长期随访结果[J].华中科技大学学报:医学版,2016,45(4):411-414
8 Wallaert A,Van LW,Hernandez L,et al.Comprehensive miRNA expression profiling in human T-cell acute lymphoblastic leukemia by small RNA-sequencing[J].Sci Rep,2017,7(1):7901
9 Shi FQ,Zhang YY,Tian XU,et al.Expression levels of miR-17-92 in peripheral blood lymphocytes of patients with refractory acute lymphocytic leukemia[J].J Leuk Lymph,2013,22(10):604-606
10 Sharifi M,Salehi R,Gheisari Y,et al.Inhibition of microRNA miR-92a induces apoptosis and inhibits cell proliferation in human acute promyelocytic leukemia through modulation of p63 expression[J].Mole Biol Rep,2014,41(5):2799-2808
11 刘景珍.儿童急性淋巴细胞白血病的预后及相关影响因素分析[J].中国妇幼保健,2014,29(1):70-72
12 Scherr M,Elder A,Battmer K,et al.Differential expression of miR-17～92 identifies BCL2 as a therapeutic target in BCR-ABL-positive B-lineage acute lymphoblastic leukemia[J].Leukemia,2014,28(3):554-565
13 Mian YA,Zeleznikle NJ.The miR-17～92 cluster contributes to MLL leukemia through the repression of MEIS1 competitor PKNOX1[J].Leuk Res,2016,46:51-60
14 Gong JN,Yu J,Lin HS,et al.The role,mechanism and potentially therapeutic application of microRNA-29 family in acute myeloid leukemia[J].Cell Death Differ,2014,21(1):100-112