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中国循证儿科杂志

中国循证儿科杂志 ›› 2017, Vol. 12 ›› Issue (1): 7-11.

• 论著 • 上一篇    下一篇

组蛋白去乙酰化酶7基因表达与儿童急性淋巴细胞白血病临床生物学特征及预后的相关性

侯贝，高超 ，刘曙光， 张瑞东 ，陆继冉， 郑胡镛   

  1. 北京儿童血液病与肿瘤分子分型北京市重点实验室，儿科学国家重点学科，儿科重大疾病研究教育部重点实验室，首都医科大学附属北京儿童医院血液肿瘤中心北京,100045
  • 收稿日期:2017-02-15 修回日期:2017-03-13 出版日期:2017-02-25 发布日期:2017-02-25
  • 通讯作者: 郑胡镛

Association of histone deacetylase 7 and the clinico-biological characteristics and outcome in childhood acute lymphoblastic leukemia

HOU Bei , GAO Chao, LIU Shu-guang , ZHANG Rui-dong , LU Ji-ran , ZHENG Hu-yong   

  1. Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics, Ministry of Education; MOE Key Laboratory of Major Diseases in Children; Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China
  • Received:2017-02-15 Revised:2017-03-13 Online:2017-02-25 Published:2017-02-25
  • Contact: ZHENG Hu-yong

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摘要：

目的：探讨组蛋白去乙酰化酶7（HDAC7）基因在急性淋巴细胞白血病（ALL）患儿骨髓标本中的表达及其与临床特征、早期治疗反应和长期预后的关系。 方法：纳入2010年1月1日至2012年12月30日首都医科大学附属北京儿童医院（我院）血液肿瘤中心收治的ALL患儿，排除入院前曾不规则使用激素和初诊骨髓样本中幼稚细胞比例＜70%的患儿。采用实时定量PCR（RT-qPCR）检测ALL患儿初诊骨髓标本中的HDAC7基因表达。以3例ALL患儿停药3年以上处于缓解状态的骨髓样本中的HDAC7表达水平作为对照，将ALL患儿分为高表达（≥1.0）组和低表达（＜1.0）组，分析组间临床生物学特征、微小残留病和无事件生存率（EFS）。 结果：共纳入236例ALL患儿，初诊骨髓标本中HDAC7基因表达水平为0.046~10.581，高表达组124例，低表达组112例。单因素分析显示HDAC7基因表达与初诊外周血WBC＜50×109·L-1 、免疫表型和融合基因类型相关，P均＜0.05；多因素分析显示WBC＜50×109·L-1 和融合基因类型是HDAC7表达的影响因素，P均＜0.05。中危ALL患儿中，HDAC7高表达组的预后好于低表达组，5年EFS分别为（91.0±3.5）%和（75.5±4.9）%，P=0.013，HDAC7表达是中危患儿的独立预后因素（P=0.013），OR值和95%置信区间为1.26（1.31~9.51）。 结论：ALL患儿骨髓中HDAC7基因表达水平与临床和生物学特征相关；HDAC7基因低表达是中危患儿预后不良的独立危险因素。

Abstract:

Objective:To discuss the of histone deacetylase 7(HDAC7) in bone marrow samples of patients with newly diagnosed pediatric acute lymphoblastic leukemia (ALL) and the association with clinic-biological characteristics, early treatment responses and long-term outcome.Methods: The HDAC7 level of pediatric patients with newly diagnosed ALL was determined by RT-qPCR method. Three samples from ALL patients in CCR for more than 3 years after treatment were used as control and patients were divided into high-（≥1.0） and low- （<1.0）groups．The differences of clinico-biological characteristics, minimal residual disease and event-free survival (EFS) were analyzed between high and low groups. Results: HDAC7 of 236 pediatric patients with newly diagnosed ALL ranged from 0.046 to 10.581, with 124 and 112 patients in the high group and low group, respectively. Univariate analysis showed that the of HDAC7 was associated with low peripheral white blood count （WBC） at diagnosis（＜50×109·L-1 ）, pro-B immunophenotype and MLL gene rearrangement（all P＜0.05）. Logistic multivariate regression analysis showed that WBC （＜50×109·L-1 ）and fusion gene were influence factors of HDAC7 （all P＜0.05）. Intermediate risk group patients with high- of HDAC7 was associated with a favorable 5 year EFS compared with low- group, with（91.0±3.5）% vs. （75.5±4.9）%，P=0.013. Furthermore, HDAC7 was indentified as the independent prognostic factor for EFS in IR patients, with odd ratio and 95% confidence interval of 1.26（1.31~9.51）. Conclusion: In pediatric ALL, of HDAC7 was found to be related to clinical and biological characteristics. Low-HDAC7 was independent adverse prognostic factor for EFS in IR subgroup.