成人t(8;21)急性髓系白血病患者初诊Ki-67的表达特征及预后意义

Abstract

目的:研究成人t(8; 21)急性髓系白血病(AML)初诊Ki-67抗原的表达特征及预后意义。方法:采集2012年7月至2019年2月本院57例成人初诊t(8; 21) AML患者的新鲜骨髓标本,采用流式细胞术(FCM)检测CD34和Ki-67抗原,分析Ki-67表达与患者初诊生物学特征、疗效及复发的关系。结果:全部患者中,CD34~+Ki-67~+细胞比例的中位值为30. 5%(范围:10. 0%～65. 8%);通过受试者工作特征(ROC)曲线确定CD34~+Ki-67~+细胞比例的最适分界阈值,CD34~+Ki-67~+细胞高比例与初诊c-KIT基因突变阳性及WT1转录本低水平均明显相关(P=0. 001; P=0. 042)。随访的36例患者中,CD34~+Ki-67~+高比例比低比例患者具有明显更高的1年累积复发(CIR)率(P=0. 035);此外,初诊WT1转录本低水平和微小残留病(MRD)高水平(2个疗程巩固治疗后RUNX1-RUNX1T1转录本水平下降<3-log)均与更高的1年CIR率明显相关(P <0. 0001;P=0. 041),初诊c-KIT基因突变阳性和白细胞计数> 10×109/L的患者分别有较高的1年CIR率趋势(P=0. 091; P=0. 054)。联合分组显示,MRD高水平同时CD34~+Ki-67~+细胞高比例的患者比其他患者具有明显更高的1年CIR率(P <0. 0001)。结论:初诊骨髓高比例的CD34~+Ki-67~+可能是成人t(8; 21) AML患者预后不良因素,MRD联合初诊CD34~+Ki-67~+细胞比例可能比单纯MRD更好地预测复发。

Objective: To investigate the characteristics and prognostic significance of Ki-67 antigen expression at diagnosis in adult t(8; 21) acute myeloid leukemia(AML). Methods: Bone marrow samples of 57 adult t(8; 21) AML patients were collected at diagnosis from July 2012 to February 2019 in our hospital,their frequencies of Ki-67 in CD34~+cells were detected by flow cytometry method,and the relationships between Ki-67 and the biological characteristics,therapeutic effect and relapse were analyzed. Results: Of all patients tested,the median percentage of CD34~+Ki-67~+cells were 30. 5%(range: 10. 0% ～ 65. 8%); A receiver operating characteristic(ROC) curve was used to identify the optimal cutoff levels of CD34~+Ki-67~+cells,higher frequencies of CD34~+Ki-67~+cells were significantly related to higher rate of c-KIT mutation and lower WT1 transcript level at diagnosis(P = 0. 001; P = 0. 042). Of all patients followed up,higher frequency of CD34~+Ki-67~+cells was significantly related to a higher 1-year cumulative incidence relapse(CIR) rate(P = 0. 035). In addition,both lower WT1 transcript level at diagnosis and higher level of minimal residual diseases(MRD,< 3-log reduction of the RUNX1-RUNX1 T1 transcript level after the second consolidation therapy) were significantly related to a higher 1-year CIR rate(P < 0. 000 1; P = 0. 041),and patients with c-KIT mutation and white blood cell count > 10 × 109/L at diagnosis tended to have higher 1-year CIR rates,respectively(P = 0. 091; P = 0.054). Patients simultaneously with high frequency of CD34~+Ki-67~+cells and high MRD levels have a significantly higher 1-year CIR rate than others(P < 0. 000 1). Conclusion: In adult patients with t(8; 21)AML,high frequency of CD34~+Ki-67~+cells at diagnosis may be a poor prognostic factor,combination of MRD levels and frequency of CD34~+Ki-67~+cells at diagnosis may better predict relapse than MRD alone.