C-KIT-D816V、NPM1基因突变在急性髓系白血病中的临床意义
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摘要
目的探讨C-KIT-D816V、NPM1与AML患者临床特征、疗效及预后相关性。方法回顾性分析南昌大学第一附属医院血液科2011年3月-2013年4月152例初诊的AML患者临床资料。结果 AML患者C-KIT-D816V基因突变表达在异常核型组明显高于正常核型组,在M2亚型发生率高于其它亚型组;C-KIT-D816V基因突变组较阴性组早期死亡率显著升高,总生存期明显缩短。AML患者NPM1基因突变表达在正常核型组明显高于异常核型组。在M2、M5亚型发生率高于其它亚型;NPM1基因突变组较阴性组CR率显著升高,总生存期延长。结论 C-KIT-D816V基因突变是AML患者预后评估差的指标之一;NPM1是AML患者预后评估较好的指标之一。
Objective To discuss on FLT3-ITD,C-KIT-D816 V mutation AML patients with the clinical features,efficacy and prognosis. Methods A retrospective analysis the clinical datas of 152 newly diagnosed AML patients were all from the hematology department of the first affiliated hospital of Nanchang University during March 2011 to April 2013. Results C-KIT-D816 V mutation occured in abnormal karyotype group was significantly higher than that in normal karyoty. It occured more often in M2 FAB subtype than others. C-KIT-D816 V mutation group had higher early mortality,shorter OS with statistical significance. NPM1 mutation occured in normal karyotype group was significantly higher than that in abnormal karyotype. It occured more often in M2,M5 FAB subtype than others. The NPM1 mutation alone group had significantly higher CR rate and longer OS. Conclusion C-KIT-D816 V mutation is one indicator of poor prognosis in AML patient. AML patients with NPM1 mutation showed good prognosis.
Objective To discuss on FLT3-ITD,C-KIT-D816 V mutation AML patients with the clinical features,efficacy and prognosis. Methods A retrospective analysis the clinical datas of 152 newly diagnosed AML patients were all from the hematology department of the first affiliated hospital of Nanchang University during March 2011 to April 2013. Results C-KIT-D816 V mutation occured in abnormal karyotype group was significantly higher than that in normal karyoty. It occured more often in M2 FAB subtype than others. C-KIT-D816 V mutation group had higher early mortality,shorter OS with statistical significance. NPM1 mutation occured in normal karyotype group was significantly higher than that in abnormal karyotype. It occured more often in M2,M5 FAB subtype than others. The NPM1 mutation alone group had significantly higher CR rate and longer OS. Conclusion C-KIT-D816 V mutation is one indicator of poor prognosis in AML patient. AML patients with NPM1 mutation showed good prognosis.
引文
[1]Mrozek K,Heinonen K,Bloomfield CD.Clinical importance of cytogenetics in acute myeloid leukaemia[J].Best Pract Res Clin Haematol,2001,14(1):19-47.
[2]张之南.血液病诊断及疗效标准[J].第3版.北京:科学出版社.2007.106-112.
[3]Fuster O,Barragan E,Bolufer P,et al.Rapid detection of KIT mutations in core-binding factor acute myeloid leukemia using high-resolution melting analysis[J].J Mol Diagn,2009,11(5):458-463.
[4]Falini B,Mecucci C,Tiacci E,et al.Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype[J].N Engl J Med,2005,352(3):254-266.
[5]Verhaak RG,Goudswaard CS,van Putten W,et al.Mutations in nucleophosmin(NPM1)in acute myeloid leukemia(AML):associa￣tion with other gene abnormalities and previously established gene expression signatures and their favorable prognostic significance[J].Blood,2005,106(12):3747-3754.
[6]Suzuki T,Kiyoi H,Ozeki K,et al.Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia[J].Blood,2005,106(8):2854-2861.
[7]Chen W,Rassidakis GZ,Medeiros LJ.Nucleophosmin gene mutations in acute myeloid leukemia[J].Arch Pathol Lab Med,2006,130(11):1687-1692.
[8]Thiede C,Koch S,Creutzig E,et al.Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia(AML)[J].Blood,2006,107(10):4011-4020.
[9]颜灵芝,陈苏宁,梁建英,等.急性髓系白血病患者NPM1基因突变分析[J].中华血液学杂志,2007,28(5):289-293.
[10]Schlenk RF,Dohner K,Krauter J,et al.Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia[J].N Engl J Med,2008,358(18):1909-1918.
[11]孙超,夏珺,张苏江,等.正常核型急性髓系白血病NPM1基因突变的临床研究[J].山东医药,2011(12):17-20.
[12]邹积艳,朱平,张立鹏,等.伴有NPM1基因突变的急性髓细胞白血病患者的临床特征[J].中华临床医师杂志(电子版),2010(11):2121-2126.
[13]Dohner K,Schlenk RF,Habdank M,et al.Mutant nucleophosmin(NPM1)predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics:interaction with other gene mutations[J].Blood,2005,106(12):3740-3746.
[14]Schnittger S,Schoch C,Kern W,et al.Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogen￣ous leukemia with a normal karyotype[J].Blood,2005,106(12):3733-3739.
[15]丁子轩,沈宏杰,缪竞诚,等.C-kit、NPM1、FLT3基因突变在656例中国急性髓系白血病患者中的分布及其对预后的影响[J].中华血液学杂志,2012,33(10):829-834.
[2]张之南.血液病诊断及疗效标准[J].第3版.北京:科学出版社.2007.106-112.
[3]Fuster O,Barragan E,Bolufer P,et al.Rapid detection of KIT mutations in core-binding factor acute myeloid leukemia using high-resolution melting analysis[J].J Mol Diagn,2009,11(5):458-463.
[4]Falini B,Mecucci C,Tiacci E,et al.Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype[J].N Engl J Med,2005,352(3):254-266.
[5]Verhaak RG,Goudswaard CS,van Putten W,et al.Mutations in nucleophosmin(NPM1)in acute myeloid leukemia(AML):associa￣tion with other gene abnormalities and previously established gene expression signatures and their favorable prognostic significance[J].Blood,2005,106(12):3747-3754.
[6]Suzuki T,Kiyoi H,Ozeki K,et al.Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia[J].Blood,2005,106(8):2854-2861.
[7]Chen W,Rassidakis GZ,Medeiros LJ.Nucleophosmin gene mutations in acute myeloid leukemia[J].Arch Pathol Lab Med,2006,130(11):1687-1692.
[8]Thiede C,Koch S,Creutzig E,et al.Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia(AML)[J].Blood,2006,107(10):4011-4020.
[9]颜灵芝,陈苏宁,梁建英,等.急性髓系白血病患者NPM1基因突变分析[J].中华血液学杂志,2007,28(5):289-293.
[10]Schlenk RF,Dohner K,Krauter J,et al.Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia[J].N Engl J Med,2008,358(18):1909-1918.
[11]孙超,夏珺,张苏江,等.正常核型急性髓系白血病NPM1基因突变的临床研究[J].山东医药,2011(12):17-20.
[12]邹积艳,朱平,张立鹏,等.伴有NPM1基因突变的急性髓细胞白血病患者的临床特征[J].中华临床医师杂志(电子版),2010(11):2121-2126.
[13]Dohner K,Schlenk RF,Habdank M,et al.Mutant nucleophosmin(NPM1)predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics:interaction with other gene mutations[J].Blood,2005,106(12):3740-3746.
[14]Schnittger S,Schoch C,Kern W,et al.Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogen￣ous leukemia with a normal karyotype[J].Blood,2005,106(12):3733-3739.
[15]丁子轩,沈宏杰,缪竞诚,等.C-kit、NPM1、FLT3基因突变在656例中国急性髓系白血病患者中的分布及其对预后的影响[J].中华血液学杂志,2012,33(10):829-834.