骨髓增生异常综合征患者的asxli基因变异分析

目的探讨骨髓增生异常综合征(myelodysplastic syndromes,MDS)患者ASXL1基因变异的发生情况及其与其他基因变异和部分临床参数之间的相关性。方法采用PCR扩增产物直接测序法检测149例MDS患者ASXU、U2AF1、SF3B1、DNMT3A、TET2、IDH1/2、NPM1、FLT3-ITD.C-KIT等基因的变异情况。结果在149例患者中,ASXU基因变异的检出率为24.8%(37/149),变异率>5%的基因分别是U2AF1(22.8%)、TET2(11.4%)、DNMT3A(9.4%)、NPM1(8.1%).SF3B1(6.0%)。ASXL1变异最常见的共存变异基因为U2AF1(27.0%,10/37)及TET2(18.9%,7/37)。ASXL1变异组与野生组患者在中位年龄、MDS亚型、染色体核型、外周白细胞、血红蛋白、血小板水平及骨髓原始细胞计数等方面的差异均无统计学意义(P>0.05)o对29例ASXL1变异患者进行了有效的随访,其中11例进展为急性髓系白血病(acute myeloid leukemia,AML),白血病转化率为37.9%。在92例野生型患者中,13例进展为AML,白血病转化率为14.1%。ASXL1变异组白血病转化率明显高于野生组,差异有统计学意义(PV 0.01)。结论ASXL1变异在MDS中有较高的发生率,并常与U2AF1及TET2基因变异共存,伴有该变异的患者具有更高的白血病转化率。

Analysis of ASXLI gene variant in patients with myelodysplastic syndrome

Objective To detect ASXLI gene variants among patients with myelodysplastic syndrome(MDS)and explore their correlation with variants of other genes and clinical features of patients.Methods For 149 patients with MDS,genomic DNA was amplified by PCR and subject to direct sequencing to identify variants of ASXLI,U2AF1,SF3B1,DNMT3A,TET2,IDH1/2,NPM1 f FLT3-ITD and C-KIT genes.Results ASXLI variants were found among 37 patients(24.8%).Other commonly mutated genes included U2AF1(22.8%),TET2(11.4%),DNMT3A(9.4%),NPM1(&1%)and SF3B1(6.0%).The frequency of concurrent U2AF1 and TET2 variants among patients with ASXLI variants was slightly higher than that of wild-type patients.No significant difference was found in median age,MDS subtype,karyotype,peripheral leukocytes,hemoglobin,platelet levels,and bone marrow blast counts between the ASXLI-variant and the wild-type groups(P>0.05).Twenty-nine patients harboring ASXLI variants were followed up,37.9%progressed to acute myeloid leukemia(AML).The rate of transformation in ASXLI-variant group was significantly higher than the wild-type group(37.9%vs.14.1%,P<0.01).Conclusion ASXL1 showed a high&equency of variant among MDS patients,which was frequently accompanied with U2AF1 and TET2 variants.Compared with the wild type group,patients with ASXL1 variants were more likely to progress to AML.