急性单核细胞白血病患者分子遗传学特征分析  

Analysis on molecular genetic characteristics of acute monocytic leukemia patients

作　　者：刘洁[1] 周民[1] 晁红颖[1] 姜乃可[1] 卢绪章[1] 

机构地区：[1]常州市第二人民医院,213003

出　　处：《中国实用医药》2016年第36期4-7,共4页China Practical Medicine

摘　　要：目的综合检测急性单核细胞白血病（AML-M5）患者DNMT3A、FLT3-ITD、NPM1等基因突变发生情况,初步探讨AML-M5患者的分子遗传学特征。方法采用基因组DNA-聚合酶链反应（PCR）扩增产物直接测序法检测NPM1基因12号外显子、c-KIT基因8、17号外显子、DNMT3A热点突变、CEBPA全部编码区及FLT3基因14、15号外显子中ITD的突变发生情况;荧光原位杂交（FISH）检测MLL重排发生情况;多重PCR检测29种常见白血病融合基因发生情况。结果①82例患者异常核型检出率为37.80%（31/82）,其中涉及11q23者占48.39%（15/31）。15例11q23异常患者经FISH检测均发现MLL重排阳性,该组患者平均年龄47.1岁,平均外周白細胞水平59.03×10^9/L,经常规化疗方案诱导后完全缓解（CR）率40.00%（6/15）。其他异常核型占51.61%（16/31）,平均年龄32.3岁,平均外周白细胞水平13.41×10^9/L,CR率为56.25%（9/16）。正常核型51例,平均年龄43.3岁,平均外周白细胞水平42.74×10^9/L,CR率为76.47%（39/51）。不管何种染色体核型异常CR率比较差异无统计学意义（P〉0.05）,正常核型患者CR率高于11q23异常患者（P〈0.05）。②70例进行基因突变检测的AMLM5患者中,48.57%的患者具有一种及以上基因突变,依次为FLT3-ITD（30.00%）、DNMT3A（24.29%）、NPM1（17.14%）、CEBPA（8.57%）、c-KIT（1.43%）。③正常核型中基因突变比例明显高于11q23重排患者,差异具有统计学意义（P〈0.05）,不同基因突变发生年龄、性別及CR率有一定的差异。结论11q23是AML-M5患者最为常见的染色体核型异常,伴此种异常者预后不良。基因突变的总发生率48.75%,以FLT3-ITD突变多见,而CEBPA、c-KIT基因突变则是AML-M5中较少见的基因异常,突变在正常核型患者中常见,其与临床特点及疗效有一定的相关性。Objective To comprehensively detect gene mutation of DNMT3A, FLT3-ITD and NPM1 in acute monoeytic leukemia （AML-M5） patients, for preliminary discussion molecular genetic characteristics in AML-M5 patients. Methods Occurrence of gene mutation in exon 12 of NPM1 gene, exon 8 and exon 17 of c-KIT gene, hot spot mutation of DNMT3A, all coding regions of CEBPA, exon 14 and exon 15 of FLT3 gene were detected by genomic DNA-polymerase chain reaction （PCR） amplification product direct sequencing method. Occurrence of MLL rearrangement was detected by fluorescence in situ hybridization （FISH）, and 29 kinds of common leukemia fusion gene were detected by multiple PCR detection. Results ① 82 patients had abnormal karyotype detection rate as 37.80% （31/82）, including 48.39% （15/31） of 11q23 cases. 15 patients with abnormal 11q23 all had detected MLL rearrangement by FISH, with average age as 47.1 years old, mean peripheral white blood cell level as 59.03 × 10^9/L, adn complete remission （CR） rate after induction of conventional chemotherapy regimens as 40.00% （6/15）. The other abnormal karyotype accounted for 51.61% （16/31）, wih average age as 32.3 years old, mean peripheral white blood cell level as 13.41×10^9/L, and CR rate as 56.25% （9/16）. There were 51 normal karyotype cases, with average age as 43.3 years old, mean peripheral white blood cell level as 42.74 × 10^9/L, CR rate as 76.47% （39/51）. There was no statistically significant difference in CR rate of all types of abnormal chromosome karyotype （P〉0.05）, and the normal karyotype patients had higher CR rate than abnormal 11q23 patients （P〈0.05）. ② Among 70 AML-M5 patients received gene mutations detection, 48.57% of patients had one or more than one kind of gene mutations, with FLT3-ITD （30.00%）, DNMT3A （24.29%）, NPM1 （17.14%）, CEBPA （8.57%）, and c-KIT （1.43%） in order. ③Normal karyotype had higher Gene mutation ratio than 11q23 rearrangement patients, and the difference had statistica

关 键 词：急性单核细胞白血病 突变基因 核型 

分 类 号：R733.71[医药卫生—肿瘤]