SIRT1在急性髓系白血病患儿骨髓活检组织中的表达及临床意义

Expression of SIRT1 in bone marrow biopsy tissues and its clinical significance among children with acute myeloid leukemia

摘要:

目的 了解SIRTl 在急性髓系白血病（AML）患儿骨髓活检组织中的表达水平，并分析其与AML 预后的相关性。方法 回顾性分析2009 年7 月至2012 年4 月确诊为AML 并于初诊时行骨髓活检检查的54 例患儿的临床资料。采用免疫组织化学染色方法检测患儿骨髓活检组织中SIRTl 的表达；根据SIRT1 的表达情况将病例分为SIRT1 阴性组（n=10）和SIRT1 阳性组（n=44），再根据SIRT1 表达的阳性程度进一步将SIRT1 阳性组分为（+）组（n=8）、（2+）组（n=7）和（3+）组（n=29），比较各组患儿的预后。Cox 多因素回归分析患儿长期生存的危险因素。结果 SIRT1（3+）组病死率明显高于SIRT1 阴性组（P<0.05）。SIRT1 阳性组2 年总生存率低于SIRT1 阴性组（P<0.05）；2 年无事件生存率亦低于SIRT1 阴性组（P<0.05）。Cox 多因素回归分析显示SIRT1 阳性表达不利于患儿的长期生存（P=0.045，危险系数绝对值=2.071，95%CI：1.017~4.219）。结论 部分AML患儿骨髓活检组织存在SIRTl表达增高情况，且SIRTl高表达与不良预后相关。

Abstract:

Objective To determine the expression level of silent mating-type information regulation 2 homologue 1 (SIRT1) in bone marrow biopsy tissues among children with acute myeloid leukemia (AML) and analyze its relationship with the prognosis of AML patients. Methods A retrospective analysis was performed on the clinical data of 54 children who were diagnosed with AML between July 2009 and April 2012 and who underwent bone marrow biopsy at diagnosis. The expression of SIRT1 in bone marrow was measured by immunohistochemistry. The 54 patients were divided into two groups according to the expression of SIRT1: SIRT1-negative (n=10) and SIRT1- positive (n=44). The SIRT1-positive group was further divided into three subgroups: SIRT1(+) (n=8), SIRT1(++) (n=7) and SIRT1(+++) (n=29) according to the expression levels of SIRT1. Cox multivariate regression analysis was used to determine the unfavorable factors for long survival in children with AML. Results The SIRT1(+++) subgroup had a significantly higher mortality than the SIRT1-negative group (P<0.05). Compared with the SIRT1-negative group, the SIRT1-positive group had a significantly lower 2-year overall survival rate (P<0.05) and a significantly lower 2-year event-free survival rate (P<0.05). Cox multivariate regression analysis showed that positive expression of SIRT1 was an unfavorable factor for long-term survival in children with AML, with a risk coefficient of 2.071 (95% CI: 1.017-4.219; P=0.045). Conclusions SIRT1 is overexpressed in some of pediatric AML patients, and the overexpression of SIRT1 is associated with poor prognosis.