DLC-1基因启动子甲基化对于B-ALL的预后价值

Prognostic significance of DLC-1 gene promoter methylation in B-ALL

目的观察儿童急性淋巴细胞白血病中肝癌缺失-1(DLC-1)抑癌基因启动子甲基化状态,评估该基因甲基化对于急性B淋巴细胞白血病(B-ALL)的预后价值。方法对40例B-ALL患儿DLC-1启动子甲基化状态与白血病敏感预后指标白血病微小残留病灶(MRD),以及其他对B-ALL预后可能有影响的指标作一比较,评价DLC-1对于B-ALL的预后判断价值,以及是否可以作为B-ALL的独立预后危险因素。结果 DLC-1甲基化阳性的B-ALL患儿的复发率和5年无事件生存率均与DLC-1甲基化阴性患儿差异有统计学意义(P<0.05)。DLC-1启动子甲基化与MRD的结果分布并不一致(P>0.05)。但两者同为阳性结果的5例患儿在5年内全都复发,复发率为100%;而两者同为阴性结果的11例患儿,仅1例在5年内复发,复发率为9%。多因素分析显示仅MRD可作为独立的预后危险因素(P=0.017),DLC-1基因甲基化阳性患儿复发风险是甲基化阴性患儿的8.5倍。结论 DLC-1甲基化和MRD都是B-ALL有意义的预后指标,两者结合可为临床提供覆盖面更广的预后信息。DLC-1甲基化也显示了该指标有成为独立预后危险因素的趋势。

Objective To observe the status of the deleted in liver cancer-1（DLC-1） gene promoter methylation and estimate the prognostic value in patients with childhood B-cell acute lymphoblastic leukemia（B-ALL）.Methods The prognostic significance of DLC-1 methylation status in B-ALL was determined by analyzing the associations among DLC-1 methylation status and the sensitive prognostic factor minimal residual disease（MRD） as well as other potential prognostic factors from 40 patients with childhood B-ALL for evaluating whether it could be an independent risk factor.Results The B-ALL patients with DLC-1 gene methylation had significant different relapse rate and event-free survival rate from those without DLC-1 gene methylation（P0.05）.The distribution of the results from DLC-1 methylation status and MRD was significantly different（P0.05）.However,all 5 patients with both MRD and DLC-1 gene methylation positive relapsed in 5 years（relapse rate 100%）.Only 1 case relapsed in 5 years in 11 patients with the results of both MRD and DLC-1 gene methylation negative（relapse rate： 9%）.Multivariable analysis showed that only MRD was a risk factor for the prognosis（P=0.017）.The relapse risk of patients with DLC-1 gene methylation was 8.5 times higher than that of patients without DLC-1 gene methylation.Conclusions Both MRD and DLC-1 gene methylation are good markers for the prognosis of B-ALL.The combination of these 2 markers could provide wider coverage of information for prognosis assessment.DLC-1 gene methylation also shows the trends of being an independent risk factor for the prognosis.