CAJ | 학술논문

目的探讨核苷类似物代谢相关基因NT5C2在儿童急性白血病(AL)患者骨髓样本中的表达及其临床意义.方法采用实时荧光定量PCR和免疫组织化学染色法检测63例初诊、15例完全缓解和7例复发AL患儿NT5C2 mRNA及蛋白水平,以16例非恶性血液系统疾病患儿作为对照.分析NT5C2在AL患儿中的表达及其与临床指标的关系.结果 ①NT5C2mRNA在初诊急性B淋巴细胞白血病(B-ALL)、急性T淋巴细胞白血病(T-ALL)、急性髓系白血病(AML)和对照组的表达水平分别为1.16 (0.89～2.25)、0.96(0.74～1.25)、1.66(0.84～3.15)和0.88 (0.61～1.21).其中AML (P＜0.01)、B-ALL(P＜0.05)的表达水平显著高于对照组;T-ALL的表达水平与对照组相比差异无统计学意义(P＞0.05).动态观察NT5C2 mRNA在15例AL患儿不同治疗阶段的表达变化,完全缓解后表达水平明显降低(P＜0.01).复发AL患儿的NT5C2 mRNA水平显著高于缓解组及对照组(P＜0.01).②免疫组织化学染色检测显示NT5C2蛋白水平与mRNA水平趋势一致.③在AML、T-ALL患儿组中NT5C2mRNA表达水平与危险度分级呈正相关(r值分别为0.434、0.389,P值均＜0.05).④NT5C2高表达组AML患儿的诱导缓解化疗第9天骨髓不缓解率(35.2％对0)、巩固治疗前骨髓不缓解率(25.0％对0)、微小残留病阳性率(36.4％对14.3％)和复发率(38.5％对28.6％)均高于低表达组,但差异无统计学意义(P值均＞0.05).结论 NT5C2高表达是儿童AL预后不良相关危险因素,有望成为指导个体化化疗、判断预后、监测复发的指标.
목적 탐토핵감유사물대사상관기인NT5C2재인동급성백혈병(AL)환자골수양본중적표체급기림상의의.방법 채용실시형광정량PCR화면역조직화학염색법검측63례초진、15례완전완해화7례복발AL환인NT5C2 mRNA급단백수평,이16례비악성혈액계통질병환인작위대조.분석NT5C2재AL환인중적표체급기여림상지표적관계.결과 ①NT5C2mRNA재초진급성B림파세포백혈병(B-ALL)、급성T림파세포백혈병(T-ALL)、급성수계백혈병(AML)화대조조적표체수평분별위1.16 (0.89～2.25)、0.96(0.74～1.25)、1.66(0.84～3.15)화0.88 (0.61～1.21).기중AML (P＜0.01)、B-ALL(P＜0.05)적표체수평현저고우대조조;T-ALL적표체수평여대조조상비차이무통계학의의(P＞0.05).동태관찰NT5C2 mRNA재15례AL환인불동치료계단적표체변화,완전완해후표체수평명현강저(P＜0.01).복발AL환인적NT5C2 mRNA수평현저고우완해조급대조조(P＜0.01).②면역조직화학염색검측현시NT5C2단백수평여mRNA수평추세일치.③재AML、T-ALL환인조중NT5C2mRNA표체수평여위험도분급정정상관(r치분별위0.434、0.389,P치균＜0.05).④NT5C2고표체조AML환인적유도완해화료제9천골수불완해솔(35.2％대0)、공고치료전골수불완해솔(25.0％대0)、미소잔류병양성솔(36.4％대14.3％)화복발솔(38.5％대28.6％)균고우저표체조,단차이무통계학의의(P치균＞0.05).결론 NT5C2고표체시인동AL예후불량상관위험인소,유망성위지도개체화화료、판단예후、감측복발적지표.
Objective To investigate the expression level and analyze the clinical significance of NT5C2,which is an nucleoside analogues metabolism related gene,in children with acute leukemia(AL).Methods Real-time PCR and immunohistochemistry were presented to detect the level ofNT5C2 mRNA and its protein product cN-Ⅱ in bone marrow samples of 63 patients initially diagnosed with AL,15 patients who achieved complete remission,7 patients who relapsed and 16 non-hematologic malignancie controls.The expression of NT5C2 mRNA in different groups of AL and its relevance with clinical indicators were analyzed.Results ①The expression of NT5C2 mRNA in newly diagnosed B-ALL,TALL,AML and controls were 1.16(0.89-2.25),0.96(0.74-1.25),1.66(0.84-3.15) and 0.88(0.61-1.21),respectively.NT5C2 mRNA expression in AML (P＜0.01)and B-ALL (P＜0.05) cases were higher than that in controls;NT5C2 mRNA expression in T-ALL and in controls showed no significant difference (P＞0.05).Changes of NT5C2 mRNA level were observed between preliminary diagnosis and complete remission in 15 patients.NT5C2 mRNA levels were significantly decreased in complete remission stage than that in newly diagnosis AL (P＜0.01).NT5C2 rmRNA levels of relapsed-refractory group were higher than that of complete remission group and controls (P＜0.01).②Immunohistochemical staining results revealed that NT5C2 protein levels were consistent with the trend of mRNA levels.③NT5C2 mRNA levels in AML (r=0.434) and T-ALL (r=0.389)were positively correlated with risk classification (P＜0.05).④ During chemotherapy of patients with AML,the NR rate of bone marrow in NT5C2 high expression group was higher than that of low expression group after 9 days induction chemotherapy (35.2％ vs 0) and before consolidation therapy (25.0％ vs 0);The positive rate of minimal-residual disease (36.4％ vs 14.3％)and relapse rate of AL (38.5％ vs 28.6％) were increased in NT5C2 high expressed patients than that in low expressed patients,but all the differences were insignificant (P＞0.05).Conclusions High expression of NT5C2 was found to be a related risk factor of AL children with unfavourable prognosis.NT5C2 promises a new target for guiding individualized chemotherapy and evaluating the prognosis of childhood acute leukemia and monitoring recurrence.