目的：探讨骨髓增生异常性肿瘤（myelodysplastic syndrome, MDS）患者基因突变与临床特征、预后及急性髓系白血病(acute myeloid leukemia, AML)转化风险间的相关性。方法：回顾性分析100例连续的初治MDS患者的临床资料，采用第二代测序技术检测患者中34种MDS疾病相关突变基因，分析该队列中不同基因的突变发生率及分布情况，探讨高频基因突变(突变率≥10%)与患者临床特征、预后及转化为AML风险之间的关系。结果：100例MDS患者共检出32种基因突变，有84%患者出现至少1种基因突变，基因突变最多见于MDS伴多系病态造血（MDS with multilineage dysplasia， MDS-MLD）患者(39.3%)；≥60岁老年患者中有82.8%（53/64）出现基因突变。基因突变中，ASXL1突变发生率最高(26.0％)，其他突变率大于10％的基因（高频基因）还包括TET2、U2AF1、DNMT3A、RUNX1、TP53和SF3B1。ASXL1易与RUNX1共突变，与TP53突变共排斥。在基因突变与临床特征相关性分析中，ASXL1突变组骨髓原始细胞比例高于ASXL1未突变组；U2AF1突变组血小板计数少于U2AF1未突变组，老年患者中DNMT3A突变(85.7%)高于年轻患者(14.3%)；RUNX1突变组白细胞计数高于RUNX1未突变组；TP53突变组中位国际预后评分系统-修订版（International Prognostic Scoring System-Revised， IPSS-R）评分(6.0分)高于TP53未突变组(4.5分)，P=0.016；TP53突变组中位乳酸脱氢酶（lactate dehydrogenase, LDH）数值(420 U/L)高于TP53未突变组(222 U/L) (P=0.002)。本研究中位随访时间为18.6个月，中位生存时间27.1个月，多因素分析表明，TP53突变是总体生存期（overall survival，OS）短的独立危险因素。随访期间，15例(15%)患者发生AML转化，而DNMT3A基因突变是MDS患者发生AML转化的独立危险因素（HR=3.73）。结论：本研究中MDS患者的MDS相关基因突变率为84%，TP53突变与患者不良预后有关，DNMT3A突变与患者易于发生AML转化有关。

Objective To investigate the correlation between gene mutations and clinical features, prognosis, and the risk of acute myeloid leukemia (AML) transformation in patients with myelodysplastic syndrome (MDS). Methods We retrospectively analyzed clinical data from 100 MDS patients and next-generation sequencing（NGS） was employed to identify 34 MDS-associated gene mutations across all patients. The mutation rates and distributions were analyzed to assess the correlation of high-frequency mutations (≥10%) with clinical features, prognosis, and the risk of AML progression. Results NGS identified 32 types of gene mutations across the cohort, with 84% of patients harboring at least one mutation. Mutations were most frequently observed in the MDS-MLD subtypes (39.3%) and predominantly in patients aged ≥60 years（82.8%，53/64）. The ASXL1 gene exhibited the highest mutation ratio (26%), with TET2, U2AF1, DNMT3A, RUNX1, TP53, and SF3B1 also showing incidence higher than 10%. ASXL1 frequently co-mutated with RUNX1 and with TP53 exclusion. It revealed that higher percentages of bone marrow blasts were seen in ASXL1-positive patients, lower platelet counts in U2AF1-positive patients, and a greater prevalence of DNMT3A mutations in elderly patients (85.7%). RUNX1 mutations were associated with elevated white blood cell counts, while TP53 mutations correlated with higher IPSS-R scores（6 vs 4.5）(P=0.016 )and elevated LDH levels（P=0.002）（420 U/L vs 222 U/L）, respectively. The median follow-up period was 18.6 months, and the median overall survival was 27.1 months, with TP53 mutations being an independent predictor for poor overall survival (OS). During follow-up, 15% of patients progressed to AML, with DNMT3A mutations identified as an independent risk factor for AML transformation（HR=3.73）. Conclusions Genetic mutations are prevalent in MDS and correlate with distinct clinical features. In this cohort of MDS patients, the mutation rate of MDS-related genes is 84%. TP53 mutations were associated with poor prognosis, whereas DNMT3A mutations are linked to an increased risk of AML transformation.