Dao F T, Yang L, Wang Y Z, Chang Y, Jiang Q, Jiang H, Liu Y R, Huang X J, Qin Y Z
Peking University Peoples'Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing 100044, China.
Zhonghua Xue Ye Xue Za Zhi. 2019 Oct 14;40(10):831-836. doi: 10.3760/cma.j.issn.0253-2727.2019.10.007.
To investigate the characteristic and prognostic significance of leukemia stem cells associated antigens expressions including CD34, CD38, CD123, CD96 and TIM-3 in t (8;21) AML. Bone marrow samples of 47 t (8;21) AML patients were collected at diagnosis from October 2015 to April 2018 in Peking University Peoples' Hospital, then flow cytometry method was performed to detect the expression frequencies of CD34, CD38, CD123, CD96 and TIM-3 to analyze the relationship between leukemia stem cells associated antigens expressions and relapse. Of 47 t (8;21) AML patients tested, the median percentages of CD34(+)CD38(-), CD34(+) CD38(-)CD123(+), CD34(+)CD38(-) CD96(+) and CD34(+) CD38(-) TIM-3(+) cells among nucleated cells were 2.37%, 0.24%, 0.27% and 0.06%, respectively. All the frequencies of CD34(+)CD38(-), CD34(+)CD38(-)CD123(+), CD34(+)CD38(-)CD96(+) and CD34(+) CD38(-)TIM-3(+) cells had no impact on the achievement of CR after the first course of induction. All higher frequencies of CD34(+)CD38(-), CD34(+)CD38(-)CD123(+), CD34(+)CD38(-)CD96(+) cells were related to higher 2-year CIR rate. Whereas, the frequency of CD34(+) CD38(-) TIM-3(+) cells had no impact on CIR rate. Both high frequency of CD34(+) CD38(-) cells and the high level of minimal residual diseases (patients with <3-log reduction in the RUNX1-RUNX1T1 transcript level after the second consolidation therapy) were independent poor prognostic factors of CIR[=0.025, =6.9 (95% 1.3-37.4) ; =0.031, =11.1 (95% 1.2-99.2) ]. Different leukemia stem cells associated antigens had distinct prognostic significance in t (8;21) AML. High frequencies of CD34(+) CD38(-), CD34(+) CD38(-) CD123(+) and CD34(+)CD38(-)CD96(+) cells at diagnosis predicted relapse in patients with t (8;21) AML.
探讨t(8;21)急性髓系白血病(AML)中白血病干细胞相关抗原CD34、CD38、CD123、CD96和TIM-3表达的特征及其预后意义。2015年10月至2018年4月,在北京大学人民医院收集47例初诊t(8;21)AML患者的骨髓样本,采用流式细胞术检测CD34、CD38、CD123、CD96和TIM-3的表达频率,分析白血病干细胞相关抗原表达与复发的关系。在47例检测的t(8;21)AML患者中,有核细胞中CD34(+)CD38(-)、CD34(+)CD38(-)CD123(+)、CD34(+)CD38(-)CD96(+)和CD34(+)CD38(-)TIM-3(+)细胞的中位百分比分别为2.37%、0.24%、0.27%和0.06%。首次诱导疗程后,CD34(+)CD38(-)、CD34(+)CD38(-)CD123(+)、CD34(+)CD38(-)CD96(+)和CD34(+)CD38(-)TIM-3(+)细胞的所有频率对达到完全缓解(CR)均无影响。CD34(+)CD38(-)、CD34(+)CD38(-)CD123(+)、CD34(+)CD38(-)CD96(+)细胞的所有较高频率均与2年累积复发率(CIR)较高相关。而CD34(+)CD38(-)TIM-3(+)细胞的频率对CIR无影响。CD34(+)CD38(-)细胞的高频率和微小残留病的高水平(第二次巩固治疗后RUNX1-RUNX1T1转录水平降低<3个对数的患者)均为CIR的独立不良预后因素[=0.025,=6.9(95% 1.3 - 37.4);=0.031,=11.1(95% 1.2 - 99.2)]。不同的白血病干细胞相关抗原在t(8;21)AML中具有不同的预后意义。诊断时CD34(+)CD38(-)、CD34(+)CD38(-)CD123(+)和CD34(+)CD38(-)CD96(+)细胞的高频率预示t(8;21)AML患者复发。