张艳,高华强,华海应,朱文艳,周晔,王志清,张苏江,仇红霞
ZHANG Yan,GAO Huaqiang,HUA Haiying,ZHU Wenyan,ZHOU Ye,WANG Zhiqing,ZHANG Sujiang,QIU Hongxia

• 1:南京医科大学第一附属医院江苏省人民医院血液科
• 2:无锡市第三人民医院血液科

摘要(Abstract)：

目的:探讨急性髓系白血病(AML)患者CEBPA基因突变的发生率,分析伴CEBPA突变的正常核型AML(NK-AML)患者的临床特征及预后。方法:80例AML初发患者,以基因组DNA为模板,分两段扩增整个CEBPA基因,扩增产物测序检测CEBPA突变,分析NK-AML中CEBPA突变型组及野生型组患者总生存(OS)、无事件生存(EFS)。结果:检出CEBPA基因突变10例,突变率为12.5%(10/80),均为M2型,核型正常;突变主要为N端移码突变和C端框内突变;CEBPA突变型组患者初诊时外周血小板计数明显低于野生型组,差异有统计学意义(P<0.05),CEBPA突变型组患者OS、EFS与CEBPA野生型组,差异无统计学意义(P>0.05)。结论:CEBPA基因突变多见于正常核型AML-M2患者,伴CEBPA突变患者初诊时外周血血小板计数较低,但不影响预后。
Objective: To explore the incidence of CEBPA gene mutation in patients with acute myeloid leukemia( AML),and to study the clinical features and prognosis of normal karyotype AML( NKAML) patients with CEBPA gene mutation. Methods: The entire CEBPA coding region of 80 AML primary patients was amplified using genomic DNA as template and sequenced. The overall survival rates( OS) and event free survival rates( EFS) of NK-AML patients in mutation group and wild type group were analyzed. Results: CEBPA mutations were found in 10 patients,and mutation rate was 12. 5 %( 10/80). All the 10 patients were M2 and NK-AML. The mutations mainly were N-terminal nonsense mutations and C-terminal in-frame mutation. Compared with wild type patients,the patients with CEBPA mutations had lower platelet counts( P < 0. 05). The OS and EFS of AML patients with CEBPA mutation were similar to patients without CEBPA mutation( P > 0. 05). Conclusions: CEBPA mutations are mainly identified in NK-AML patients with M2 subtype. CEBPA mutant cases are associated with lower platelet counts,but not affect prognosis.

关键词(KeyWords)： 基因,CEBPA;突变;白血病,粒细胞,急性;核型分析;血小板
gene,CEBPA;mutation;leukemia,myeloid,acute;karyotype analysis;platelet

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81070456,81270652)

作者(Author): 张艳,高华强,华海应,朱文艳,周晔,王志清,张苏江,仇红霞
ZHANG Yan,GAO Huaqiang,HUA Haiying,ZHU Wenyan,ZHOU Ye,WANG Zhiqing,ZHANG Sujiang,QIU Hongxia

DOI: 10.19367/j.cnki.1000-2707.2014.05.012

参考文献(References)：

• [1]Kelly LM,Gilliland DG.Genetics of myeloid leukemias[J].Annu Rev Genomics Hum Genet,2002(3):179-198.
• [2]Mueller BU,Pabst T.CEBPA and the pathophysiology of acute myeloid leukemia(AML)[J].Curr Opin Hematol,2006(13):7-14.
• [3]张之南,沈悌.血液病诊断及疗效标准[M].3版.北京:科学出版社,2007:106-115.
• [4]Martelli MP,Sportoletti P,Tiacci E,et al.Mutational landscape of AML with normal cytogenetics:biological and clinical implications[J].Blood Rev,2013(27):13-22.
• [5]Pabst T,Mueller BU.Transcriptional dysregulation during myeloid transformation in AML[J].Oncogene,2007(26):6829-6837.
• [6]Preudhomme C,Sagot C,Boissel N,et al.for the ALFA Group.Favorable prognostic significance of CEBPA mutations in patients with de novo acute myeloid leukemia:a study from the Acute Leukemia French Association(ALFA)[J].Blood,2002(100):2717-2723.
• [7]Pabst T,Mueller BU.Complexity of CEBPA dysregulation in human acute myeloid leukemia[J].Clin Cancer Res,2009(15):5303-5307.
• [8]Han C,Lin D,Ai XF,et al.CEBPA gene mutation analysis in acute myeloid leukemia[J].Chin J Hematol,2013(34):566-571.
• [9]杜雅哲,苏龙,李薇,等.正常核型急性髓系白血病CEBPA基因突变患者临床特征及疗效研究[J].中国实验血液学杂志,2014(22):16-19.
• [10]Pabst T,Mueller BU,Zhang P,et al.Dominant-negative mutations of CEBPA encoding CCAAT/enhancer binding protein alpha(CEBPA),in acute myeloid leukemia[J].Nat Genet,2001(27):263-270.
• [11]Leroy H,Roumier C,Huyghe P,et al.CEBPA point mutations in hematological malignancies[J].Leukemia,2005(19):329-334.
• [12]Wouters BJ,Louwers I,Valk PJ,et al.A recurrent inframe insertion in a CEBPA transactivation domain is a polymorphism rather than a mutation that does not affect gene expression profilingbased clustering of AML[J].Blood,2007(109):389-390.
• [13]Lin LI,Chen CY,Lin DT,et al.Characterization of CEBPA mutations in acute myeloid leukemia:most patients with CEBPA mutations have biallelic mutations and show a distinct immunophenotype of the leukemic cells[J].Cllin Cancer Res,2005(11):1372-1379.
• [14]Walter RB,Othus M,Burnett AK,et al.Significance of FAB subclassification of"acute myeloid leukemia,NOS"in the 2008 WHO classification:analysis of 5848 newly diagnosed patients[J].Blood,2013(121):2424-2431.
• [15]Frohling S,Schlenk RF,Stolze I,et al.Mutations in younger adults with acute myeloid leukemia and normal cytogenetics:prognostic relevance and analysis of cooperating mutations[J].J Clin Oncol,2004(22):624-633.

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