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Abstract：
Objective: To explore the clinical and prognostic values of TP53 gene mutation in patients with acute myeloid leukemia (AML) . Methods: A retrospective analysis of 265 newly diagnosed AML patients with next-generation sequencing (NGS) data in the Hematology Department of Changhai Hospital from January 2010 to January 2019 was performed. Mutation analysis was carried out by targeted sequencing technology including 200 hematological malignancy related genes. The association of TP53 mutation with clinical features was analyzed. Results: Alterations in TP53 were found in 20 (7.5%) patients, including 17 case (6.4%) of missense mutations, 2 cases (0.7%) of frame-shift deletion mutations and 1 case (0.4%) of splicing sites mutation. A total of 23 kinds of TP53 mutations were detected, most of them (16, 69.6%) were located in the DNA binding domain of exon 5-8, 4 in the DNA binding domain of exon 3-4, 2 in exon 10 and 1 in splice site, respectively. The median age of patients with TP53 alterations was higher than those without [52 (26-72) years old vs 45 (14-75) years old, P= 0.008]. The frequency of complex karyotypes was higher in patients with TP53 alterations than those without [45.0% (9/20) vs 6.1% (15/245) , P<0.001]. Median overall survival (OS) of patients with TP53 alterations was shorter than those without[14.1 (95%CI 6.78-21.42) months vs 31.4 (95%CI 13.20-49.59) months, P=0.029]. The OS of patients treated with \"Decitabine + CAG\" was superior than that of patients treated with \"3 + 7\" regimen [30.0 (95%CI 27.35-38.84) months vs 12.5 (95%CI 5.80-19.19) months, P=0.018]. Multivariate analysis indicated that TP53, DNMT3A and USH2A alterations, WBC ≥ 12.45×10(9)/L had negative impacts on OS. Conclusion: The frequency of TP53 mutation was 7.5% in our cohort. Most mutations were located in the DNA binding domain. TP53 alterations were strongly associated with older age, complex karyotype and shorter OS. Decitabine-based induction chemotherapy and hematopoietic stem cell transplantation may improve OS, more cases and/or multicenter randomized studies are needed for further confirmation.
目的： 探讨伴TP53基因异常急性髓系白血病（AML）患者的临床特征及预后。 方法： 回顾性分析2010年1月至2019年1月上海长海医院血液科新诊断的有初发靶向二代测序（NGS）数据的265例AML患者临床资料。采用包含210个血液肿瘤相关基因的靶向测序技术进行突变分析。分析TP53基因突变和（或）缺失与临床特征之间的关系及其对患者生存的影响。 结果： 20例（7.5%）患者伴TP53基因异常，其中错义突变17例（6.4%），移码（缺失）基因突变2例（0.7%），剪切位点突变1例（0.4%）。共检测到23种TP53基因突变，其中4个位于DNA结合结构域第3~4号外显子，16个位于DNA结合结构域第5~8号外显子，2个位于第10号外显子，1个为剪切子突变。伴TP53基因异常患者平均突变基因个数（6.2个）与无TP53基因异常组（6.4个）差异无统计学意义（P=0.770）。TP53基因异常患者的中位年龄为52（26~72）岁，高于无TP53基因异常患者的45（14~75）岁（P=0.008）；复杂核型比例（45.0%，9/20）显著高于无TP53异常组（6.1%，15/245）（P<0.001）；中位总生存（OS）时间[14.1（95%CI 6.78~21.42）个月]较无TP53异常组[31.4（95%CI 13.20~49.59）个月]显著缩短（P=0.029）。20例伴TP53基因异常患者中4例采用\"地西他滨+CAG\"方案诱导治疗，15例采用\"3+7\"方案治疗，中位生存时间分别为30.0个月和12.5个月（P=0.018）。多因素分析中，TP53、DNMT3A、USH2A基因异常及初发WBC>12.45×10(9)/L是影响OS的独立预后不良因素。 结论： 伴TP53基因异常AML患者中错义突变常见，突变位点主要分布于DNA结合结构域。TP53基因异常与高龄、复杂核型相关，且常与多个基因突变相伴出现。以地西他滨为基础的诱导化疗及异基因造血干细胞移植可能会提高患者生存率。.
目的： 探讨伴TP53基因异常急性髓系白血病（AML）患者的临床特征及预后。 方法： 回顾性分析2010年1月至2019年1月上海长海医院血液科新诊断的有初发靶向二代测序（NGS）数据的265例AML患者临床资料。采用包含210个血液肿瘤相关基因的靶向测序技术进行突变分析。分析TP53基因突变和（或）缺失与临床特征之间的关系及其对患者生存的影响。 结果： 20例（7.5%）患者伴TP53基因异常，其中错义突变17例（6.4%），移码（缺失）基因突变2例（0.7%），剪切位点突变1例（0.4%）。共检测到23种TP53基因突变，其中4个位于DNA结合结构域第3~4号外显子，16个位于DNA结合结构域第5~8号外显子，2个位于第10号外显子，1个为剪切子突变。伴TP53基因异常患者平均突变基因个数（6.2个）与无TP53基因异常组（6.4个）差异无统计学意义（P=0.770）。TP53基因异常患者的中位年龄为52（26~72）岁，高于无TP53基因异常患者的45（14~75）岁（P=0.008）；复杂核型比例（45.0%，9/20）显著高于无TP53异常组（6.1%，15/245）（P<0.001）；中位总生存（OS）时间[14.1（95%CI 6.78~21.42）个月]较无TP53异常组[31.4（95%CI 13.20~49.59）个月]显著缩短（P=0.029）。20例伴TP53基因异常患者中4例采用\"地西他滨+CAG\"方案诱导治疗，15例采用\"3+7\"方案治疗，中位生存时间分别为30.0个月和12.5个月（P=0.018）。多因素分析中，TP53、DNMT3A、USH2A基因异常及初发WBC>12.45×10(9)/L是影响OS的独立预后不良因素。 结论： 伴TP53基因异常AML患者中错义突变常见，突变位点主要分布于DNA结合结构域。TP53基因异常与高龄、复杂核型相关，且常与多个基因突变相伴出现。以地西他滨为基础的诱导化疗及异基因造血干细胞移植可能会提高患者生存率。.
摘要：
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