伴BCOR/BCORL1突变的髓系肿瘤共突变基因表达谱及病理参数分析

Analysis of co-mutation gene expression spectrum and pathological parameters in myeloid malignancies with BCOR/BCORL1 mutation

目的探讨BCOR/BCORL1突变的髓系肿瘤患者的共突变基因表达谱,分析其病理参数及临床意义。方法回顾性分析2017年1月至2021年8月在上海交通大学附属第一人民医院确诊的47例BCOR/BCORL1突变的髓系肿瘤患者。运用二代测序技术分析患者的基因共突变表达谱,采用两独立样本秩和检验分析BCOR/BCORL1突变患者病理参数之间的差异。通过Kaplan-Meier分析突变位置和治疗方法对患者无病生存(DFS)时间和总生存(OS)时间的影响。结果急性髓系白血病(AML)患者以点突变为主(51.1%),骨髓增生异常综合征(MDS)和MDS/骨髓增殖性肿瘤(MPN)患者以移码突变、错义突变和无义突变为主(19.1%),二者分布差异具有统计学意义(χ^(2)=7.458,P=0.006)。伴代谢酶组突变患者白细胞计数(Z=-3.500,P=0.018)、血小板计数(Z=82.500,P=0.027)、血浆纤维蛋白原(Fib)含量(Z=-0.935,P=0.008)和凝血酶时间(Z=0.800,P=0.027)与野生型患者相比差异均有统计学意义;伴甲基化组突变患者血浆Fib含量(Z=-0.855,P=0.030)、伴信号传导通路组突变患者的白细胞计数(Z=5.500,P=0.019)和转录因子组突变患者凝血酶原时间(Z=-1.600,P=0.008)与野生型患者相比差异有统计学意义。结构域突变患者中位DFS时间明显短于非结构域突变患者(χ^(2)=4.920,P=0.027)。与未移植组患者相比,移植组患者中位DFS时间和中位OS时间显著延长(χ^(2)=7.703,P=0.006;χ^(2)=13.380,P=0.000)。结论BCOR/BCORL1突变的髓系肿瘤患者的共突变基因与白细胞计数、血浆Fib等临床病理参数密切相关。异基因造血干细胞移植可有效改善此类突变患者预后。

Objective To investigate the co-mutation gene expression spectrum of myeloid malignancy patients with BCOR/BCORL1 mutation,and analyze its pathological parameters and clinical significance.Methods Forty-seven myeloid malignancy patients with BCOR/BCORL1 mutation diagnosed in the First People′s Hospital Affiliated to Shanghai Jiaotong University during January 2017 and August 2021 were analyzed retrospectively.The co-mutation gene expression spectrum of the patients was analyzed by the next generation sequencing technology,and the correlation of mutations with pathological parameters was analyzed by the Mann-Whitney test.The effects of mutation location and treatment methods on the disease-free survival(DFS)time and overall survival(OS)time of the patients were evaluated by the Kaplan-Meier analysis.Results The patients with AML were mainly with point mutations(51.1%)of BCOR/BCORL1/matati,while the patients with MDS and MDS/MPN were mainly with frameshift mutations,missense mutations and nonsense mutations of BCOR/BCORL1/matati(19.1%,χ^(2)=7.458,P=0.006).There were significant differences in white blood cell(WBC)count(Z=-3.500,P=0.018),platelet count(Z=82.500,P=0.027),plasma fibrinogen(Fib)level(Z=-0.935,P=0.008)and thrombin time(Z=0.800,P=0.027)between the patients with metabolic enzyme-related gene mutations and with wild-type.The plasma Fib level of patients with methylation-related gene mutations(Z=-0.855,P=0.030),WBC count of patients with signaling transduction pathway-related gene mutations(Z=5.500,P=0.019)and prothrombin time of patients with transcription factor-related gene mutations(Z=-1.600,P=0.008)were significantly different from those of patients with wild-type.The median DFS time of patients with domain mutation was significantly shorter than that of patients with non-domain mutation(χ^(2)=4.920,P=0.027).The median DFS time and OS time of the patients in the transplantation group were significantly longer than that in the non-transplantation group(χ^(2)=7.703,P=0.006;χ^(2)=13.380,P=0.000).Conclusion The co-mutation genes in myeloid malignancy patients with BCOR/BCORL1 mutation are closely related to the pathological parameters of the patients,such as WBC count,plasma Fib level and etc.Allogeneic hematopoietic stem cell transplantation can effectively improve the prognosis of patients with such mutations.