骨髓增生异常综合征患者DNMT3A基因突变的情况及临床意义

Frequency and clinical significance of DNMT3A gene mutations in patients with MDS

目的:了解DNMT3A基因突变在骨髓增生异常综合征(MDS)患者中的发生率、分布情况及临床意义。方法:选取2012年4月至2018年6月在湘雅二医院和湘潭市中心医院住院的85例MDS患者为研究对象。提取患者外周血基因组DNA,针对DNMT3A基因突变热点R882位点设计合成引物,采用聚合酶链式反应法扩增DNMT3A基因23号外显子整个编码区基因片段,再将扩增产物纯化后测序,分析DNMT3A基因突变在本组患者中的发生率、分布情况及临床意义。结果:85例MDS患者中检测到5例DNMT3A基因突变,突变阳性率5.9%,其中R882H和R882C基因突变各2例,R882P基因突变1例,未见R882S基因突变。常规化疗联合去甲基化药物地西他滨治疗后,1例患者一度获得血液学完全缓解,复杂染色体核型恢复正常,但是1月后转为急性白血病并发严重感染死亡,1例治疗后稳定,2例治疗后疾病进展,1例死于肺部感染。结论:MDS中DNMT3A基因突变率低,其突变多预示预后较差,并可能更快地向急性髓性白血病转化,选择去甲基化药物治疗可能获益。

Objective:To evaluate the frequency,distribution and clinical significance of DNMT3A gene mutations in patients with myelodysplastic syndrome(MDS).Methods:85 MDS patients from Second Xiangya Hospital and Xiangtan Central Hospital were enrolled in this study.Genome DNA samples were extracted from patients'peripheral blood cells.Specific primers spanning the mutational hotspot-R882 in DNMT3A were designed and synthesized,then polymerase chain reaction was used to amplify encoding DNA fragments on the 23rd exome of DNMT3A.Subsequently,the amplified products were purified and sequenced.Results:Of all the 85 MDS patients,2 cases with R882H and 2 cases with R882C in DNMT3A were detected.R882P mutation in DNMT3A was detected in 1 of 85 MDS patients.All of the 5 cases harboring DNMT3A mutations were treated with conventional chemotherapy combined with demethylation drug-decitabine.A case harboring R882H mutation once reached a complete hematologic remission.However,one month later,he progressed to acute leukemia and died from severe infection.A case harboring R882H mutation reached a disease-stable situation.2 case harboring R882C mutation suffered from disease progression.A case harboring R882P mutation died from severe infection.Conclusion:DNMT3A gene mutation is a rare event in MDS patients,and it predicts a poor prognosis with rapid transformation to acute leukemia.Patients with DNMT3A gene mutation may benefit from demethylation drug.