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SET基因在急性髓系白血病患者中的表达及其临床意义 被引量:4

Expression level of SET gene in acute myeloid leukemia and its clinical significance
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摘要 目的 研究SET基因在急性髓系白血病(AML)患者中的表达水平及其临床意义.方法 采用实时定量PCR方法检测141例初发AML患者骨髓单个核细胞SET基因表达水平,并分析其与临床特征和疗效的关系.结果 141例初发AML患者均检测到SET基因的表达,中位表达水平为0.86(0.02~15.69).SET基因表达水平与性别、年龄、骨髓原始细胞比例、血红蛋白水平、血小板计数、FAB分型及NPM1和FLT3-ITD基因突变、染色体核型等无明显相关性(P值均>0.05),但SET基因高表达组高白细胞(≥100×109/L)患者比例为31.0%,明显高于SET基因低表达组(11.4%,P=0.005).141例AML患者中136例接受化疗,SET基因高表达组2个疗程完全缓解(CR)率(50.0%)显著低于SET基因低表达组(73.5%,P=0.005).SET基因高表达组的中位总生存(OS)和无事件生存(EFS)时间分别为10和2个月,明显短于低表达组(分别为22和14个月,P值分别为0.001和0.005);多因素COX模型分析显示,SET基因高表达是AML患者OS独立不良预后因素(P=0.002);此外,在正常核型AML患者中,SET基因高表达组的中位OS时间、EFS时间分别为12和4个月,短于低表达组(分别为35和14个月),差异有统计学意义(P值分别为0.010和0.026).结论 SET基因高表达与AML不良预后相关,SET基因高表达可能是AML患者的不良预后分子标志. Objective To investigate the expression level of SET gene in patients with acute myeloid leukemia (AML) and evaluate its significance. Methods The expression level of SET gene in 141 de novo AML patients was determined by real time quantitative PCR (RQ-PCR), and its relationship with the clinical features and outcomes of these patients were analyzed. Results SET gene transcript level was detected in 141 AML patients with the median expression level of 0.86 (range 0.02- 15.69). AML patients with higher SET gene expression had a higher level of white blood cell (WBC~〉100x 109/L) count than of lower SET gene expression ones (31.0% vs 11.4%, P=-0.005). In the 136 patients who received treatment after diagnosis, higher SET gene expression group had lower complete remission rate (50.0%) than of lower expression cohort (73.5%) after two cycles of chemotherapy (P=0.005). Survival analysis showed that patients with higher SET gene expression had significantly shorter overall survival (OS) (10 months vs 22 months, P=0.001) and event-free survival(EFS) (2 months vs 14 months, P=-0.005) than of lower SET gene expression ones. Multivariate COX regression analysis showed SET overexpression was an independent prognostic factor for OS. In the patients with the normal karyotype, higher SET expression group also had significantly shorter OS (12 months vs 35 months, months, P=0.026) than of lower SET expression ones. Conclusion P=0.010) and EFS (4 months vs 14 High expression of SET gene was associated with poor prognosis and might be a prognostic molecular marker of AML.
出处 《中华血液学杂志》 CAS CSCD 北大核心 2014年第5期397-402,共6页 Chinese Journal of Hematology
基金 卫生公益性行业科研专项(201202017) 浙江省重点创新团队(2011R50015) 浙江省卫生厅医药卫生科技计划项目(2008B088)
关键词 基因 SET 白血病 髓样 急性 预后 Gene, SET Leukemia, myeloid, acute Prognosis
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参考文献23

  • 1Seo SB, McNamara P, Heo S, et al. Regulation of histone acetylation and transcription by INHAT, a human cellular complex containing the set oncoprotein [ J ]. Cell, 2001, 104 ( 1 ): 119-130.
  • 2Kutney SN, Hong R, Macfarlan T, et al. A signaling role of histone-binding proteins and INHAT subunits pp32 and Set/TAF- Ibeta in integrating ehromatin hypoacetylation and transcriptional repression [J]. J Biol Chem, 2004, 279 (29): 30850-30855.
  • 3Kandilci A, Mientjes E, Grosveld G. Effects of SET and SET- CAN on the differentiation of the human promonocytic cell line U937 [J]. Leukemia, 2004, 18(2):337-340.
  • 4Canela N, Rodriguez-Vilarrupla A, Estanyol JM, et al. The SET protein regulates G2/M transition by modulating cyclin B-cyclin- dependent kinase 1 activity [J]. J Biol Chem, 2003, 278 (2): 1158-1164.
  • 5Cervoni N, Detich N, Seo SB, et al. The oncoprotein Set/TAF- lbeta, an inhibitor of histone acetyltransferase, inhibits active demethylation of DNA, integrating DNA methylation and transcriptional silencing [J]. J Biol Chem, 2002, 277 (28): 25026-25031.
  • 6成人急性髓系白血病(非急性早幼粒细胞白血病)中国诊疗指南(2011年版)[J].中华血液学杂志,2011,32(11):804-807. 被引量:180
  • 7von Lindem M, van Baal S, Wiegant J, et al. Can, a putative oncogene associated with myeloid leukemogenesis, may be activated by fusion of its 3' half to different genes: characterization of the set gene[J]. Mol Cell Biol, 1992, 12(8): 3346-3355.
  • 8Adachi Y, Pavlakis GN, Copeland TD, et al. Identification and characterization of SET, a nuclear phosphoprotein encoded by the translocation break point in acute undifferentiated leukemia [J]. J Biol Chem, 1994, 269(3):2258-2262.
  • 9Fan Z, Beresford P J, Oh DY, et al. Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-mediated apopto- sis, and the nucleosome assembly protein SET is its inhibitor [J]. Cell, 2003, 112(5):659-672.
  • 10A1-Murrani SW, Woodgett JR, Damuni Z. Expression of I2PP2A, an inhibitor of protein phosphatase 2A, induces c-Jun and AP-1 activity[J]. Biochem J, 1999, 341 (Pt 2):293-298.

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  • 1王慧君,王建祥.正常核型急性髓系白血病预后因素的研究进展[J].中华血液学杂志,2007,28(6):428-431. 被引量:1
  • 2吴德沛,颜灵芝,杨莉,陈苏宁,吴小津,梁建英.急性髓细胞白血病患者NPM1与FLT3基因突变的研究[J].中华内科杂志,2007,46(11):907-910. 被引量:10
  • 3Kharas MG, Lengner CJ, Al- Shahrour F, et al. Musashi- 2regulates normal hematopoiesis and promotes aggressivemyeloid leukemia[J]. Nat Med, 2010,16(8): 903-908.
  • 4Byers RJ, Currie T, Tholouli E, et al. MSI2 protein expressionpredicts unfavorable outcome in acute myeloid leukemia [J].Blood, 2011,118(10):2857-2867.
  • 5Mu Q,Wang Y,Chen B, et al. High expression of Musashi-2indicates poor prognosis in adult B- cell acute lymphoblasticleukemia[J]. Leuk Res, 2013, 37(8): 922-927.
  • 6Levis M. FFLT3/ITD AML and the law of unintended conse-quencestJ]. Blood, 2011, 117(26): 6987-6990.
  • 7Balatzenko G,Spassov B, Stoyanov N, et al. NPM1 Gene TypeA Mutation in Bulgarian Adults with Acute Myeloid Leukemia:A Single-Institution Study [J]. Turk J Haematol, 2014, 31 (1):40-48.
  • 8Gaidzik VI,Paschka P, Spath D, et al. TET2 mutations in acutemyeloid leukemia (AML): results from a comprehensivegenetic and clinical analysis of the AML study group [J]. J ClinOncol, 2012,30: 1350-1357.
  • 9Park SM, Gonen M, Vu L, et al. Musashi2 sustains the mixed-lineage leukemia-driven stem cell regulatory program [j]. J ClinInvest, 2015, 125(3): 1286-1298.
  • 10Zhang H, Tan S, Wang J, et al. Musashi2 modulates K562leukemic cell proliferation and apoptosis involving the MAPKpathway [J]. Exp Cell Res, 2014, 320(1): 119-127.

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