TP53等位基因状态对骨髓增生异常综合征患者临床表现和预后的影响  

Effect of TP53 Allelic State on Clinical Performance and Prognosisof Patients with Myelodysplastic Syndrome

作　　者：沈凯 胡德媛 陈苏宁[1] SHEN Kai;HU De-Yuan;CHEN Su-Ning(Department of Hematology,The First Affiliated Hospital of Soochow University,Suzhou 215006,Jiangsu Province,China)

机构地区：[1]苏州大学附属第一医院血液科,江苏苏州215006

出　　处：《中国实验血液学杂志》2024年第3期811-818,共8页Journal of Experimental Hematology

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。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 independentl

关 键 词：骨髓增生异常综合征 TP53突变 等位基因状态 预后 

分 类 号：R733[医药卫生—肿瘤]