PRPS1基因在儿童急性白血病中的表达及其临床意义

摘要

目的:研究PRPS1基因在儿童急性白血病(AL)中的表达及其与该病临床特征的相关性.方法:采用实时荧光定量PCR和Western blot的方法分别检测176例儿童AL(初诊126例,完全缓解50例)中PRPS1 mRNA和蛋白的表达水平,分析其表达水平与临床特征的相关性.以21例非恶性血液病患儿骨髓作为对照.结果:①在BALL组中,PRPS1在初诊组表达水平显著高于对照组,同时高于完全缓解组(P均＜0.0001);在T-ALL及AML组中,仅在初诊组与完全缓解组中有差异(P均＜0.0001);②在B-ALLL样本中,PRPS1表达水平随危险度升高而增加(P＜0.01);在T-ALL中各危险度分层组间则无明显差异(P＞0.05);在AML样本中,仅低危组与高危组差异具有统计学意义(P＜0.05);③PRPS1高表达与B-ALL患儿的高WBC计数及MRD阳性相关(P=0.020,P=0.026);④PRPS1与之前证实的复发相关基因NT5C2表达水平呈正相关(P＜0.05).结论:PRPS1是儿童B-ALL预后不良相关危险因素,有望成为判断预后,指导个性化化疗的指标.%Objective:To investigate the correlation between the expression level of PRPS1 and the clinical characterstics in children with acute leukemia (AL).Methods:Real-time quantitative RT-PCR and Western blot were used to detect the level of PRPS1 mRNA and protein expression in bone marrow samples from 176 patients diagnosed as AL (126 cases were newly diagnosed and 50 cases in complete remission),and its relevance with clinical indicators was statistically analyzed.The bone marrow samples from 21 children with non-malignant hematological disease were used as controls.Results:(1) In B-ALL group,the level of PRPS1 mRNA in newly diagnosed patients were significantly higher than that in control and than that in complete remission patients (both P ＜ 0.0001).In T-ALL and AML group,differences was only observed between newly diagnosed patients and complete remission patients (both P ＜ 0.0001);(2)In B-ALL group,the expression level of PRPS1 increase with along risk enhancement (P ＜ 0.01),while no significant difference was observed in T-ALL (P ＞ 0.05).In AML patients,expression difference was shown between low risk group and high risk group(P ＜ 0.05);(3)High PRPS1 mRNA expression level were associated with high WBC counts and MRD positive in B-ALL patients (P =0.020,P =0.026,respectively);(4) Expression of NT5C2,an essential gene for relapse and drug resistance,was found to be positively correlated with PRPS1 expression in AL samples(P＜ 0.05).Conclusion:High expression of PRPS1 is relevant factor of unfavourable prognosis in B-ALL children,which suggest PRPS1 may be a new indicator for prognosis of pediatric B-ALL and an index to guide individualized chemotherapy.