PRPS1基因在儿童急性白血病中的表达及其临床意义

PRPS1 Expression in Children with Acute Leukemia and Its Clinical Significance

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-ALL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 characteristics in children with acute leukemia （AL）. Methods： Real-time quantitative RT-PCR and Western blot were used to detect the level of PRPS1 rnRNA 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 PRPS! may be a new indicator for prognosis of pediatric B-ALL and an index to guide individualized chemotherapy.