CAJ | 학술논문

目的探讨难治复发急性髓系白血病(AML)患者中常见的10种突变基因发生的规律.方法选取难治复发AML患者148例.基因测序检测并分析患者骨髓样本中10种常见突变基因,包括激酶类基因FLT3和KIT,转录因子基因CEBPA、NPM1和PHF6,以及表观遗传类基因ASXL1、DNMT3A、IDH1、IDH2和TET2.结果在62.16％(92/148)的患者中检测到上述基因突变阳性,其中10.14％(15/148)的患者同时携带多个基因的突变.FLT3-ITD突变率最高(19.59％,29/148),其次为KIT(12.84％,19/148)和CEBPA(11.49％,17/148)突变.KIT突变常单独出现,而IDH1/2突变常伴随其他基因突变.激酶类基因FLT3和KIT突变互斥,转录因子基因和表观遗传基因也存在同类互斥现象.以35岁为界限分组,≤35岁的患者多携带单个基因的突变[61.77％(63/102)比31.11％(14/45),P＜ 0.05],而＞35岁的患者多个基因突变(≥2个)的携带率高[20.00％(9/45)比4.90％(5/102),P＜ 0.05].＞35岁患者组中NPM1突变率高于≤35岁组[20.00％(9/45)比2.94％(3/102),P＜ 0.05].结论研究发现难治复发AML患者中常见基因突变的组合具有一定的规律,与基因的功能分类和患者的年龄有关.
목적 탐토난치복발급성수계백혈병(AML)환자중상견적10충돌변기인발생적규률.방법 선취난치복발AML환자148례.기인측서검측병분석환자골수양본중10충상견돌변기인,포괄격매류기인FLT3화KIT,전록인자기인CEBPA、NPM1화PHF6,이급표관유전류기인ASXL1、DNMT3A、IDH1、IDH2화TET2.결과 재62.16％(92/148)적환자중검측도상술기인돌변양성,기중10.14％(15/148)적환자동시휴대다개기인적돌변.FLT3-ITD돌변솔최고(19.59％,29/148),기차위KIT(12.84％,19/148)화CEBPA(11.49％,17/148)돌변.KIT돌변상단독출현,이IDH1/2돌변상반수기타기인돌변.격매류기인FLT3화KIT돌변호척,전록인자기인화표관유전기인야존재동류호척현상.이35세위계한분조,≤35세적환자다휴대단개기인적돌변[61.77％(63/102)비31.11％(14/45),P＜ 0.05],이＞35세적환자다개기인돌변(≥2개)적휴대솔고[20.00％(9/45)비4.90％(5/102),P＜ 0.05].＞35세환자조중NPM1돌변솔고우≤35세조[20.00％(9/45)비2.94％(3/102),P＜ 0.05].결론 연구발현난치복발AML환자중상견기인돌변적조합구유일정적규률,여기인적공능분류화환자적년령유관.
Objective To investigate the mutaome profiling of the 10 common mutated genes in refractory and relapsed acute myeloid leukemia (AML) patients.Methods 148 patients who were diagnosed as refractory and relapsed AML were enrolled.Mutations of 10 common mutated genes were analyzed in bone marrow samples by Sanger sequencing,including kinase genes FLT3 and KIT,transcription factor genes CEBPA,NPM1 and PHF6,as well as epigenetic regulation genes ASXL1,DNMT3A,IDH1,IDH2 and TET2.Results Mutations of the 10 genes were detected in 62.16 ％ (92/148) of the patients,and 10.14 ％ (15/148) of patients carried mutations of more than one gene.FLT3-ITD was the most frequently mutated gene,which was detected in 19.59 ％ (29/148) cases,followed by KIT (12.84 ％,19/148) and CEBPA (11.49 ％,17/148) mutations.KIT mutations usually occurred alone,while IDH1 and IDH2 often mutated accompanied with other genes.Mutations of kinase genes,including FLT3 and KIT,were mutually exclusive.Transcription factor genes and epigenetic regulation genes seldom mutated with genes of the same functional classification group.When patients were divided into two groups according to age,patients in the group of ≤ 35 years were more likely to harbor mutations of the single gene [61.77 ％ (63/102) vs 31.11％ (14/45),P ＜ 0.05],while individuals in the group of ＞ 35 years often carried mutations of more genes than one gene [20.00 ％ (9/45) vs 4.90 ％ (5/102),P ＜ 0.05].The mutation frequency of NPM1 in ＞ 35 years group was higher than that in ≤ 35 years group [20.00 ％ (9/45) vs 2.94 ％ (3/102),P ＜ 0.05].Conclusions There were certain rules in the mutaome profiling of refractory and relapsed AML patients,which was related to the function classification of genes and age of patients.