程序性死亡分子1/程序性死亡-配体1在儿童急性淋巴细胞白血病中的表达及临床意义

The expressions and clinical significance of programmed death 1/programmed death ligand 1 in children with acute lymphoblastic leukemia

目的通过检测程序性死亡分子1(PD-1)、程序性死亡-配体1(PD-L1)在急性淋巴细胞白血病(ALL)患儿骨髓单个核细胞中的表达水平,探讨PD-1/PD-L1信号通路在儿童ALL中的作用机制以及其作为潜在治疗靶点和预后预测指标的可行性,为儿童ALL的诊疗提供新思路。方法收集郑州大学第一附属医院2018年9月至2019年7月收治的59例ALL患儿骨髓标本,应用流式细胞术检测59例ALL患儿(包括初诊ALL 47例,复发ALL 12例)初诊时、诱导治疗后、早期强化治疗后骨髓单个核细胞中PD-1、PD-L1的表达,并收集患儿的相关临床资料,以同期收治的15例非恶性血液疾病患儿骨髓标本为对照组。结果PD-1在初诊组、复发组及对照组患儿骨髓单个核细胞中的表达差异无统计学意义(H=2.402,P>0.05),PD-L1在复发组[(7.32±3.60)%]和初诊组[(3.18±2.37)%]的表达率均大于对照组[(0.84±0.39)%],差异有统计学意义(H=28.048,P<0.05)。初诊组患儿骨髓单个核细胞中PD-L1在不同治疗阶段的表达:治疗前(B=1.293)>诱导治疗后(B=0.036)>早期强化治疗后(B=0.000),提示随着治疗的推进呈下降趋势;PD-L1的表达在低危组(B=-3.912)<中危组(B=-3.595)<高危组(B=0.000),提示PD-L1的表达与ALL危险程度分级有关,危险程度分级越高,PD-L1蛋白表达越高。结论PD-L1高表达可能参与儿童ALL的发病机制,不仅可作为儿童ALL的不良预测指标,还可作为化疗疗效评价指标;PD-1/PD-L1信号通路可能是儿童ALL的潜在治疗靶点。

Objective To investigate the mechanism of programmed death 1(PD-1)/programmed death ligand 1(PD-L1)signaling pathway and its feasibility as a potential therapeutic target and prognostic predictor by detecting the expressions,of PD-1 and PD-L1 in bone marrow mononuclear cells of children with acute lymphoblastic leukemia(ALL),and to provide new ideas for the diagnosis and treatment of ALL as well.Methods Bone marrow samples were collected from 59 children with ALL in the First Affiliated Hospital of Zhengzhou University from September 2018 to July 2019.Flow cytometry was applied to detect the expression of PD-1 and PD-L1 in bone marrow mononuclear cells in 59 ALL patients,including 47 newly-diagnosed ALL patients and 12 relapsed ALL patients,respectively,at initial diagnosis,after induction therapy and early intensive treatment.Their relevant clinical data were collected and compared with the bone marrow specimens of 12 children suffering from non-malignant blood diseases as the control group of the same hospital during the same period.Results There was no significant difference in the expression of PD-1 in the bone marrow mononuclear cells of the primary diagnosis group,recurrence group and control group(H=2.402,P>0.05).The expression of PD-L1 in the relapsed and refractory group[(7.32±3.60)%]and the newly diagnosed group[(3.18±2.37)%]was higher than that in the control group[(0.84±0.39)%],and the differences were statistically significant(H=28.048,P<0.05).In the initial treatment group,the expression of PD-L1 in the bone marrow mononuclear cells was the strongest expression before treatment(B=1.293),followed by after induction treatment(B=0.036)and after early intensive treatment(B=0.000),suggesting that there was a downward trend as the continued treatment.The expression of PD-L1 was the weakest expression in the low-risk group(B=-3.912)than in the medium-risk group(B=-3.595)and high-risk group(B=0.000),revealing that the expression of PD-L1 is related to the risk grades of ALL.The higher the risk rating is,the higher the PD-L1 protein expression is.Conclusions The high expression of PD-L1 may be involved in the pathogenesis and be used as an adverse predictor of ALL childhood and an evaluation index of chemotherapy efficacy.PD-1/PD-L1 signaling pathway may be a potential therapeutic target of ALL childhood.