摘要
目的监测骨髓增生异常综合征(MDS)患者去甲基化治疗后WT1 mRNA水平的变化,评估WT1 mRNA水平变化在判断患者疗效、区分不同疾病稳定(stable disease,SD)状态中的意义.方法以2009年11月至2018年3月56例在广东省人民医院接受去甲基化治疗(≥4个疗程)的MDS患者为研究对象,实时定量PCR检测其骨髓或外周血WT1 mRNA的表达,观察WT1 mRNA表达水平的动态变化与患者临床疗效和预后的相关性.结果去甲基化治疗3个疗程后,MDS患者WT1 mRNA水平较治疗前显著降低.20例疾病进展患者病情进展或转为急性髓系白血病(AML)后WT1 mRNA表达水平较治疗前明显升高.45例SD的MDS患者,根据SD期间WT1 mRNA表达水平变化分为WT1升高与未升高两组,SD期间WT1 mRNA表达水平升高的患者中病情进展或转AML的比例为95.65%(22/23),而SD期间WT1 mRNA表达水平未升高的患者中病情进展或转为AML的比例为9.09%(2/22)(X^2=33.852,P<0.001).与SD期间WT1 mRNA表达水平未升高的患者相比,SD期间WT1 mRNA表达水平升高的患者的总生存期[17(95%CI11~23)个月对未达到,P<0.001]和无进展生存期[13(95%CI8~18)个月对未达到,P<0.001]明显缩短.结论WT1 mRNA表达水平是评估MDS患者去甲基化治疗后疗效变化有效的实验室指标,尤其对于SD的患者,动态检测WT1 mRNA表达水平,可预测病情演变,从而指导临床治疗.
Objective To monitor the WT1 mRNA level and its dynamic changes in patients with myelodysplastic syndromes(MDS)after hypomethylating agents(HMA),as well as to assess the significance of WT1 mRNA levels and its dynamic changes in evaluating the efficacy of HMA and distinguishing the disease status of heterogeneous patients with stable disease(SD).Methods Bone marrow or peripheral blood samples of 56 patients with MDS who underwent hypomethylating agents(≥4 cycles)from November 2009 to March 2018 were tested by real-time quantitative polymerase chain reaction(PCR)to detect the expression of WT1 mRNA,and to observe the correlation between the dynamic changes of WT1 mRNA expression and clinical efficacy and prognosis of patients.Results WT1 mRNA expression levels of MDS patients decreased significantly after 3 cycles of hypomethylating agent treatment.Besides,the WT1 mRNA expression levels of patients increased significantly after diseases progression.According to the dynamic changes of WT1 mRNA expression levels during SD,45 cases could be further divided into increased group and non-increased group.In those SD patients with increased WT1 mRNA expression level,the ratio of suffering disease progression or transformation to AML was 95.65%(22/23),whereas the ratio turned to be 9.09%(2/22)for the non-increased group(x2=33.852,P<0.001).Compared with those SD patients reporting no increase in WT1 mRNA expression level,the overall survival[17(95%CI 11-23)months vs not reached,P<0.001]and progression-free survival[13(95%CI 8-18)months vs not reached,P<0.001]of those SD patients reporting increase in WT1 mRNA expression level were significantly shorter.Conclusion WT 1 mRNA expression level is a useful indicator to assess the efficacy of hypomethylating agents in MDS patients.Especially in patients with SD,detection of the changes in WT1 mRNA expression level is able to predict disease progression and help to make clinical decision.
作者
张弘扬
耿素霞
李敏明
赖沛龙
邓程新
陆泽生
黄欣
王玉连
翁建宇
杜欣
Zhang Hongyang;Geng Suxia;Li Minming;Lai Peilong;Deng Chengxin;Lu Zesheng;Huang Xin;Wang Yulian;Weng Jianyu;Du Xin(The Second School of Clinical Medicine,Southern Medical University,Guangzhou 510515,China;Guangdong Provincial People's Hospital/ Guangdong Academy of Medical Sciences,Guangzhou 510080,China;Guangdong Institute of Geriatric Medicine,Guangzhou 510080,China;School of Medicine,South China University of Technology,Guangzhou 510006,China)
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2019年第5期417-421,共5页
Chinese Journal of Hematology
基金
国家自然科学基金(81500012)
广东省科技计划(2014B020212009、2017B020230004).
