伴TET2基因突变急性髓系白血病成年患者临床特征及突变对疗效和预后的影响

目的:探讨伴TET2基因突变急性髓系白血病（AML）成年患者的临床特征以及突变对疗效和预后的影响。方法:选择2017年3月至2021年4月于济宁市第一人民医院就诊的123例初诊AML成年患者（除外急性早幼粒细胞白血病），采用二代测序方法检测包括TET2突变在内的24种AML相关基因突变情况。根据有无TET2基因突变将患者分为TET2基因突变型组及TET2基因野生型组，比较两组患者临床病理特征及近期疗效和生存差异。结果:123例患者中，28例（22.8%）检测到TET2突变。与TET2基因野生型组患者相比，TET2基因突变型组患者的年龄更高（59±15）岁比（49±16）岁， t=2.984， P=0.003]，更易出现法、美、英（FAB）协作组分型的M 4、M 5型75.0%（21/28）比51.6%（49/95）， χ2=4.838， P=0.028]，AML患者CD34阳性率更低46.4%（13/28）比72.6%（69/95）， χ2=6.685， P=0.010]；TET2基因突变更易伴发ZRSR2突变10.7%（3/28）比1.1%（1/95）， P=0.037]和NPM1突变35.7%（10/28）比17.9%（17/95）， χ2=4.008， P=0.045]，而较少伴发IDH1/2基因突变0比17.9%（17/95）， P=0.012]。两组间性别、初诊时外周血白细胞计数、血红蛋白水平、血小板计数、骨髓原始细胞比例、细胞遗传学及欧洲白血病网络（ELN）危险度分层方面差异均无统计学意义（均 P>0.05）。两组患者1个疗程化疗和去甲基化治疗的总有效率（ORR）差异均无统计学意义75.0%（12/16）比66.7%（42/63）， χ2=0.410， P=0.522；66.7%（4/6）比44.4%（8/18）， P=0.640]。TET2基因突变型组和野生型组总生存（OS）差异无统计学意义中位OS时间：23个月（95% CI 5~41个月）比35个月（95% CI 18~52个月）， P=0.498]。 结论:在AML成年患者中，TET2基因突变与高龄、M 4和M 5亚型、AML细胞低表达CD34相关。TET2基因突变易伴随ZRSR2、NPM1基因突变，而不易伴随IDH1或IDH2基因突变。TET2基因突变对未进行危险度分层AML患者的总体疗效和生存可能无显著影响。

Clinical characteristics of acute myeloid leukemia patients with TET2 gene mutation and effects of TET2 mutation on therapeutic efficacy and prognosis

Objective:To investigate clinical features of adult patients with acute myeloid leukemia (AML) with TET2 gene mutation and effects of TET2 mutation on therapeutic efficacy and prognosis.Methods:A total of 123 newly diagnosed adult AML patients (except for acute promyelocytic leukemia) admitted to Jining No.1 People's Hospital from March 2017 to April 2021 were selected. Mutations of 24 AML-related genes including TET2 mutation were detected by using second-generation sequencing technology. Patients were divided into two groups according to the presence of TET2 mutation: TET2 mutation group and TET2 wild type group. The differences in clinicopathological characteristics, short-term efficacy and survival of both groups were compared.Results:Among 123 patients, TET2 mutation was detected in 28 cases (22.8%). Compared with TET2 wild type group, the patients were older (59±15) years vs.(49±16) years, t = 2.984, P = 0.003], French-American-British (FAB) Corporative Group M 4 and M 5 subtypes were more common 75.0% (21/28) vs. 51.6% (49/95), χ2 = 4.838, P = 0.028], and the positive rate of CD34 in AML patients was lower in TET2 mutation group 46.4% (13/28) vs.72.6% (69/95), χ2 = 6.685, P = 0.010]. Moreover, TET2 mutation was more likely to be accompanied with ZRSR2 mutation 10.7% (3/28) vs. 1.1% (1/95), P = 0.037] and NPM1 mutation 35.7% (10/28) vs.17.9% (17/95), χ2 = 4.008, P = 0.045], but less likely to be accompanied with IDH1/2 mutation 0 vs.17.9% (17/95), P = 0.012]. However, there were no statistically significant differences in gender, peripheral blood leukocyte count at initial diagnosis, hemoglobin level, platelet count, bone marrow blasts ratio, cytogenetics and the European LeukemiaNet (ELN) risk stratification between the two groups (all P>0.05). In addition, there were no significant differences in the overall response rate (ORR) of 1 cycle chemotherapy 75.0% (12/16) vs. 66.7% (42/63), χ2 = 0.410, P = 0.522] and demethylation therapy 66.7% (4/6) vs. 44.4% (8/18), P = 0.640]. The difference in overall survival (OS) of both groups was not statistically significant median OS time: 23 months (95% CI 5-41 months) vs. 35 months (95% CI 18-52 months, P = 0.498]. Conclusions:In AML patients, TET2 mutation is associated with advanced age, M 4 and M 5 subtypes, and low expression of CD34 on AML blasts. TET2 mutation is commonly accompanied by ZRSR2 and NPM1 mutation, but not IDH1 or IDH2 mutation. TET2 mutation may have no significant effects on therapeutic efficacy and survival in the whole cohort of AML patients without risk stratification.