CD+4 Foxp3+调节性T淋巴细胞在儿童急性白血病中的表达及其与微小残留病的关系

摘要

Objective To study the regulatory T cells (Treg-cell) frequencies in patients with childhood acute leukemia and evaluate its clinical application value by investigating the relationship between the increasing numbers of Treg cells and minimal residual disease of leukemia (MRD), Methods Foxp3-FITC/CD25-PE/CD4-PerCP/CD3-APC four-color staining flow cytometry was established to identify Treg cells. Treg cells frequencies both in 10 healthy controls and in 33 patients with newly diagnosed childhood acute leukemia ( B-ALL 17 cases, T-ALL 9 cases, AML 7 cases) were detected. The possibility of the accumulation of Treg cells being the prognostic marker for acute leukemia was evaluated by comparing the results of Treg cells frequency with that of MRD. Results The percentage of Treg cells in CD+4 CD+3 T cells was M = 8. 09% in normal bone marrows, which was significantly different from the results in the bone marrows of newly diagnosed childhood acute leukemia ( M = 12.77% , U = 3.41, P < 0.01 ), but it showed no significantly differences among B-ALL, T-ALL and AML groups. No association was observed between the expression of Treg cells and clinical-biologic characteristics studied. In addition, Treg cells frequency in MRD positive group was significantly different from that in MRD continuously negative group ( M = 14. 74% vs M=11.3%, t =252.5,P<0.05). Conclusions Consistent with results from solid tumor, the study identifies a significantly increased numbers of Treg cells in patients with childhood acute leukemia. The situation of accumulation of Treg cells is closely associated with MRD results during chnical remission. High level of Treg cells may cause poor prognosis and increase the possibility of relapse.%目的 研究调节性T淋巴细胞(regulatory T cell,Treg)在白血病患者体内的表达情况,探讨Treg的增高与白血病疗效监测与白血病微小残留病(minimal residual disease,MRD)预后指标之间的关系.方法 建立Foxp3-FITC/CD-25PE/CD4-PerCP/CD3-APC四色流式细胞术检测Treg的方法 ;比较10例正常骨髓标本以及33例白血病初发患者[急性B淋巴细胞白血病(B-ALL)17例,急性T淋巴细胞白血病(T-ALL)9例,急性髓细胞白血病(AML)7例]骨髓标本中Treg的数量;结合56例临床缓解患者MRD监测结果 ,评估Treg作为白血病患者预后判断评价指标的价值.结果 正常骨髓组Treg占CD+4T淋巴细胞的比例中位数(M)为8.09%,初发自血病组M为12.77%,两者差异有统计学意义(U=3.41,P<0.01);而在B-ALL、T-ALL和AML组的差异无统计学意义(H=1.22,P>0.05).Treg数量与临床病理学参数无显著相关性.此外,Treg数量在MRD阳性组(M=14.74%)与MRD持续阴性组(M=11.3%)中的差异有统计学意义(t=252.5,P<0.05).结论 白血病初发患儿体内的Treg数量显著增高,且患儿中Treg表达水平与MRD有关联.高水平Treg预示白血病患儿预后较差,存在复发的可能.