DTA突变在骨髓增生异常综合征患者中的预后价值

The prognostic value of DTA gene mutations in myelodysplastic syndrome

探讨伴DTA(DNMT3A、TET2、ASXL1)基因突变骨髓增生异常综合征(MDS)患者的临床特征及DTA突变在MDS患者的预后意义。回顾性分析2015年9月至2019年12月在新疆维吾尔自治区人民医院确诊的140例初治MDS患者的临床资料,采用2代测序对34种髓系肿瘤相关基因进行检测,了解MDS患者的DTA基因突变情况及DTA基因突变对MDS患者无进展生存时间(PFS)和总生存期(OS)的影响。(1)140例MDS患者检出DTA基因突变62例(44.3%),其中修订国际预后积分系统(IPSS-R)较低危组患者DTA突变率为65.4%,明显高于较高危组(31.8%)(P=0.000)。与未突变组相比,DTA突变患者白血病转化率较低(9.7%比29.5%,P=0.004)。(2)生存分析结果显示DTA突变与无DTA突变MDS患者相比,中位PFS差异无统计学意义(P=0.787),但DTA突变患者中位OS显著短于无DTA突变患者(16个月比20个月,P=0.022)。按照IPSS-R进一步分组,结果显示DTA突变与无DTA突变患者的中位OS仅在较高危组中差异有统计学意义(15个月比18个月,P=0.034)。(3)在62例DTA突变MDS患者中,发生其他基因共突变的有60例(96.8%),对DTA以及共突变频率>10%的基因进行Cox回归分析时,DTA突变不是独立的预后因素(P>0.05)。提示DTA突变常发生于MDS疾病早期,在IPSS-R较低危组多见,白血病转化率较低。DTA突变与MDS患者的疾病进展无关,但在MDS较高危患者中预示着较差的生存,考虑与其共突变基因对预后的共同影响有关。

To investigate the clinical features and prognostic significance in myelodysplastic syndrome(MDS)patients with DTA(DNMT3A,TET2,ASXL1)mutations.Clinical characteristics of 140 patients diagnosed as de novo MDS at People's Hospital of Xinjiang Uygur Autonomous Region from September 2015 to December 2019 were retrospectively analyzed.Next-generation sequencing was used to detect 34 related genes in MDS patients.DTA mutations and the correlation with progression-free survival(PFS)and overall survival(OS)in MDS patients were evaluated.Among 140 MDS patients,DTA mutations was detected in 62(44.3%)patients.And the positive rate of DTA mutations in IPSS-R lower-risk group was 65.4%,significantly higher than that of higher-risk group(31.8%)(P=0.000).Compared with the non-mutated group,patients with DTA mutations had a lower rate of conversion to leukemia(9.7%vs.29.5%,P=0.004).Survival analysis showed that PFS in patients with DTA mutations was comparable as that in MDS patients without DTA mutations(P=0.787),but the median OS was significantly shorter(16 months vs.20 months,P=0.022).According to IPSS-R classification,the median OS in patients with and without DTA mutation was only statistically significant in the higher-risk group(15 months vs.18 months,P=0.034).Among 62 patients with DTA mutations,60(96.8%)had additional gene mutations.DTA mutations were not independent prognostic factors when mutation frequency is greater than 10%were considered in Cox regression model(P>0.05).DTA mutations often developed in the early stage of MDS,therefore they were more common in IPSS-R lower-risk subgroup which was correlated to the low rate of conversion to leukemia.In conclusion,DTA mutations are not associated with disease progression,but predict unfavorable survival when other add-on genes are mutated.