【摘要】 目的：探讨TP53等位基因状态在骨髓增生异常综合征（MDS）患者中的临床意义。方法：回顾性分析2019年1月至2021年12月在苏州大学附属第一医院进行二代测序的858例MDS患者的临床资料。结果：患者中位年龄为52岁，中位随访时间为23.8(0.4-109.6)个月。401例患者（46.7%）至少有一个染色体异常，其中，复杂核型106例，单体核型78例。共发现103例TP53突变，突变率为12%。与TP53野生型患者相比，各种类型的染色体异常情况明显更多见于TP53突变型患者（均P<0.001）。TP53突变型患者相比野生型具有更低的血红蛋白含量、更低的血小板计数和更高的骨髓原始细胞比例（均P<0.05），总生存期（OS）也明显更短。在97例可评估的患者中，33例（34%）为单等位基因TP53突变，64例是双等位基因突变。与单等位基因相比，双等位基因TP53突变亚组中患者的染色体异常比例更高，共突变数目更少。单等位基因患者的中位OS为33.6个月，而双等位基因患者仅为11.4个月（HR=2.138,95%CI:1.053-4.343,P>0.05）。TP53野生型患者的中位OS未达到，野生型、单等位基因和双等位基因TP53突变患者中位OS比较存在明显差异（P<0.001）。多因素Cox回归分析结果显示，双等位基因TP53突变为患者不良预后的独立预测因子（HR=2.808,95%CI:1.487-5.003,P=0.001)，而单等位基因TP53突变与野生型TP53不是。结论：伴TP53突变的患者预后不良，双等位基因TP53突变相比单等位基因TP53突变预后更差，并且独立地影响MDS患者的预后。更多还原

【Abstract】 Objective: To investigate the clinical significance of TP53 allelic state in patients with myelodysplastic syndromes(MDS). Methods: The clinical data of 858 MDS patients who underwent second-generation sequencing(NGS) testing in the First Affiliated Hospital of Soochow University from January 2019 to December 2021 were retrospectively analyzed. Results: The median age of the patients was 52 years old, and median follow-up time was 23.8(0.4-109.6) months. Four hundred and one patients(46.7%) had at least one chromosomal abnormality, including 106 complex karyotypes and 78 monosomal karyotypes. A total of 103 cases of TP53 mutations were identified, with a mutation rate of 12%. Compared with TP53 wild-type, various types of chromosomal abnormalities were significantly more common in patients with TP53 mutations(all P<0.001). Patients with TP53 mutations had lower hemoglobin levels, lower platelet counts and higher percentage of bone marrow primitive cell compared with TP53 wild type(all P<0.05), and significantly shorter overall survival(OS). Among 97 evaluable patients, 33 cases(34%) were mono-allelic TP53 mutation, while 64 cases were bi-allelic TP53 mutation. Patients in bi-allelic TP53 mutation subgroup had a higher proportion of chromosomal abnormalities and a lower number of co-mutations compared with mono-allelic TP53 mutation. The median OS was 33.6 months in patients with mono-allelic state and only 11.4 months in patients with bi-allelic state(HR=2.138, 95%CI: 1.053-4.343, P>0.05). Median OS was not reached in TP53 wild-type patients, and there was a significant difference in OS among TP53 wild-type, mono-allelic and bi-allelic TP53 mutation patients(P<0.001). Multivariable Cox regression analysis showed that bi-allelic TP53 was an independent predictor of poor outcomes(HR=2.808, 95%CI: 1.487-5.003, P=0.001), while mono-allelic TP53 mutation and wild-type TP53 were not. Conclusion: Patients with TP53 mutations have a poor prognosis, and bi-allelic TP53 mutations have a worse prognosis compared with mono-allelic TP53 mutations and independently affect the prognosis of MDS patients.更多还原