分化抑制因子家族在慢性髓系白血病中的表达及临床意义
Expression and clinical significance of inhibitor of differentiation family in chronic my-eloid leukemia
周静东 1解飞 1袁倩 1郭竑 1林江 1张婷娟 1钱军1
作者信息
- 1. 江苏大学附属人民医院血液科,镇江市血液病临床医学研究中心,镇江市血液系统恶性肿瘤精准诊断与治疗重点实验室(江苏省镇江市 212002)
- 折叠
摘要
目的:探索分化抑制因子(inhibitor of differentiation,ID)家族在慢性髓系白血病(chronic myeloid leukemia,CML)中的表达和启动子甲基化水平,并分析其临床意义.方法:应用定量PCR及定量甲基化特异性PCR的方法检测 2010年 1 月至 2017年 12月期间江苏大学附属人民医院就诊的非恶性血液病患者(对照组)和CML患者骨髓单个核细胞中ID2/ID3/ID4表达及ID4启动子甲基化水平,通过分组分析ID家族异常的临床意义.结果:ID2及ID3表达在CML患者中均呈现显著上调(P<0.001,P<0.05),而ID4表达在CML患者中呈现显著下调(P<0.01).其中,接受者操作特征曲线分析揭示ID2表达可作为CML鉴别的潜在分子标志物(AUC=0.895,P<0.001).CML患者中ID4启动子高甲基化概率显著高于对照组患者(P=0.001),且ID4启动子甲基化与ID4表达呈现负相关(r=-0.424,P=0.002).通过分组分析发现ID2高表达较易发生于男性患者中(P=0.040);ID4低表达/高甲基化较易发生于加速/急变期患者(P=0.003,P<0.001).此外,CML加速/急变期患者ID4表达水平低于慢性期患者(P<0.001),而ID4甲基化水平高于慢性期患者(P<0.001).通过单因素及多因素Logistic回归分析发现ID4高甲基化是CML患者疾病进展的独立危险因素(P=0.007).结论:ID家族在CML患者中表达态势不同,其中ID2/ID3表达上调;而ID4表达下调,与ID4启动子高甲基化相关.ID4表达/甲基化与CML疾病进展相关,其中ID4甲基化可能是CML疾病进展的独立危险因素.
Abstract
Objective:To explore the expression patterns of inhibitor of differentiation(ID)family in patients with chronic myeloid leukemia(CML)and analyze their clinical implications.Methods:Quantitative PCR and quantitative methylation-specific PCR were conducted to de-tect the transcript levels of ID2/ID3/ID4 and the methylation levels of ID4 in the bone marrow mononuclear cells of non-hematological ma-lignancies(acting as controls)and patients with CML treated at The Affiliated People's Hospital of Jiangsu University from January 2010 to December 2017.The clinical implications of ID family alterations were further analyzed.Results:ID2 and ID3 expression was significantly up regulated(P<0.001 and P<0.05,respectively),whereas ID4 expression was markedly down regulated in patients with CML(P<0.01).The re-ceiver operating characteristic curve demonstrated that the ID2 transcript level is a potential biomarker for distinguishing CML from controls(AUC=0.895,P<0.001).The frequency of ID4 promoter methylation in patients with CML was drastically higher than that in the controls(P=0.001).Moreover,ID4 methylation was negatively correlated with ID4 expression in patients with CML(r=-0.424,P=0.002).Clinically,CML with high ID2 expression occurred more frequently in males(P=0.040).Patients with low ID4 expression or high ID4 methylation showed a markedly higher frequency of an accelerated phase/blast crisis(P=0.003 and P<0.001,respectively).In addition,patients with CML in an accelerated phase/blast crisis exhibited markedly lower ID4 expression and higher ID4 methylation levels than those in the chronic phase(both P<0.001).Furthermore,univariate and multiple Logistic regression analyses revealed that the ID4 methylation level was an inde-pendent risk factor for CML progression(P=0.007).Conclusions:The ID family was differentially expressed in patients with CML;specifically,ID2 and ID3 expression was significantly increased,whereas ID4 expression was markedly decreased and correlated with ID4 promoter hy-permethylation.Hence,ID4 expression and methylation are confirmed to be associated with CML progression,and ID4 methylation could be an independent risk factor for CML progression.
关键词
慢性髓系白血病/分化抑制因子/表达/甲基化/临床意义Key words
chronic myeloid leukemia(CML)/inhibitor of differentiation(ID)/expression/methylation/clinical significance引用本文复制引用
基金项目
国家自然科学基金项目(82300164)
国家自然科学基金项目(82270179)
江苏省自然科学基金项目(BK20221287)
江苏省自然科学基金项目(BK20230296)
江苏省卫健委科研项目(M2022123)
镇江市社会发展项目(SH2022027)
镇江市社会发展项目(SH2023009)
出版年
2024
NETL
NSTL
万方数据