首页|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

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

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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.
Expression and clinical significance of inhibitor of differentiation family in chronic my-eloid leukemia
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.

chronic myeloid leukemia(CML)inhibitor of differentiation(ID)expressionmethylationclinical significance

周静东、解飞、袁倩、郭竑、林江、张婷娟、钱军

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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)

慢性髓系白血病 分化抑制因子 表达 甲基化 临床意义

国家自然科学基金项目国家自然科学基金项目江苏省自然科学基金项目江苏省自然科学基金项目江苏省卫健委科研项目镇江市社会发展项目镇江市社会发展项目

8230016482270179BK20221287BK20230296M2022123SH2022027SH2023009

2024

10.12354/j.issn.1000-8179.2024.20240762

中国肿瘤临床
中国抗癌协会

中国肿瘤临床

CSTPCD北大核心
影响因子：1.32
ISSN：1000-8179
年,卷(期)：2024.51(14)
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