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

刘晓明; 周剑峰; 张培红; 阮敏; 张丽; 邹尧; 陈玉梅; 竺晓凡

doi:10.7499/j.issn.1008-8830.2014.06.011

PDF(1873 KB)

HTML

中国当代儿科杂志 ›› 2014, Vol. 16 ›› Issue (6) : 614-618. DOI: 10.7499/j.issn.1008-8830.2014.06.011

论著·临床研究

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

刘晓明¹, 周剑峰¹, 张培红², 阮敏¹, 张丽¹, 邹尧¹, 陈玉梅¹, 竺晓凡¹

作者信息 +

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

LIU Xiao-Ming¹, ZHOU Jian-Feng¹, ZHANG Pei-Hong², RUAN Min¹, ZHANG Li¹, ZOU Yao¹, CHEN Yu-Mei¹, ZHU Xiao-Fan¹

Author information +

Department of Pediatrics, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking University Mediacal Colloge, Tianjin 300020, China

Aboat authors:

[1] Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes[J].Blood, 2009, 114(5): 937-951.
[2] Huffman DM, Grizzle WE, Bamman MM, et al. SIRT1 is significantly elevated in mouse and human prostate cancer[J].Cancer Res, 2007, 67(14): 6612-6618.
[3] Stunkel W, Peh BK, Tan YC, et al. Function of the SIRT1 protein deacetylase in cancer[J].Biotechnol J, 2007, 2(11): 1360-1368.
[4] Firestein R, Blander G, Michan S, et al. The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth[J].PLoS ONE, 2008, 3(4): e2020.
[5] Chen W, Bhatia R. Roles of SIRT1 in leukemogenesis[J].Curr Opin Hematol, 2013, 20(4): 308-313.
[6] Bradbury CA, Khanim FL, Hayden R, et al. Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors[J].Leukemia, 2005, 19(10): 1751-1759.
[7] 阮敏, 王雅琴, 张丽, 等. 儿童急性髓系白血病FLT3 突变临床分析:单中心研究[J].中国当代儿科杂志, 2011, 13(11): 863-866.
[8] 张之南, 沈悌. 血液病诊断及疗效标准[M]. 第3 版. 北京: 科学出版社, 2007: 19-23.
[9] Tsukimoto I, Tawa A, Horibe K, et al. Risk-stratified therapy and the intensive use of cytarabine improves the outcome in childhood acute myeloid leukemia: the AML99 trial from the Japanese Childhood AML Cooperative Study Group[J].J Clin Oncol, 2009, 27(24): 4007-4013.
[10] 张之南, 沈悌. 血液病诊断及疗效标准[M]. 第3 版. 北京: 科学出版社, 2007: 103-116.
[11] Zhang L, Zhu X, Zou Y, et al. Effect of arsenic trioxide on the treatment of children with newly diagnosed acute promyelocytic leukemia in China[J].Int J Hematol, 2011, 93(2): 199-205.
[12] K n a b e C, K r a s k a B, K o c h C, e t a l. A m e t h o d f o r immunohistochemical detection of osteogenic markers in undecalcified bone sections[J].Biotech Histochem, 2006, 81(1): 31-39.
[13] 王泰龄, 黄受方, 李维华, 等. 《全国免疫组织化学技术与诊断标准化专题研讨会》会议纪要[J].中华病理学杂志, 1996, 25(6): 7-9.
[14] Knight JR, Milner J. SIRT1, metabolism and cancer[J].Curt Opin Oncol, 2012, 24(1): 68-75.
[15] Yuan H, Wang Z, Li L, et al. Activation of stress response gene SIRT1 by BCR-ABL promotes leukemogenesis[J].Blood, 2012, 119(8): 1904-1914.
[16] Li L, Wang L, Wang Z, et al. Activation of p53 by SIRT1 inhibition enhances elimination of CML leukemia stem cells in combination with imatinib[J].Cancer Cell, 2012, 21(2): 266-281.
[17] O'Hare T, Zabriskie MS, Eiring AM, et al. Pushing the limits of targeted therapy in chronic myeloid leukaemia[J].Nat Rev Cancer, 2012, 12(8): 513-526.

Show less

文章历史 +

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.

导出引用

刘晓明, 周剑峰, 张培红, 阮敏, 张丽, 邹尧, 陈玉梅, 竺晓凡. 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[J]. 中国当代儿科杂志. 2014, 16(6): 614-618 https://doi.org/10.7499/j.issn.1008-8830.2014.06.011

LIU Xiao-Ming, ZHOU Jian-Feng, ZHANG Pei-Hong, RUAN Min, ZHANG Li, ZOU Yao, CHEN Yu-Mei, ZHU Xiao-Fan. Expression of SIRT1 in bone marrow biopsy tissues and its clinical significance among children with acute myeloid leukemia[J]. Chinese Journal of Contemporary Pediatrics. 2014, 16(6): 614-618 https://doi.org/10.7499/j.issn.1008-8830.2014.06.011