急性髓系白血病患者骨髓中ID3/ID4基因的表达及其临床意义  

Expression of ID3/ID4 gene in bone marrow of patients with acute myeloid leukemia and its clinical significance

作　　者：王芸 张婷娟[2] 赵琪 林江[3] 钱军[1] 周静东[1] WANG Yun;ZHANG Tingjuan;ZHAO Qi;LIN Jiang;QIAN Jun;ZHOU Jingdong(Department of Hematology,the Affiliated People's Hospital of Jiangsu University,Jiangsu Zhenjiang 212002,China;Department of Oncology,the Affiliated People's Hospital of Jiangsu University,Jiangsu Zhenjiang 212002,China;Laboratory Center,the Affiliated People's Hospital of Jiangsu University,Jiangsu Zhenjiang 212002,China)

机构地区：[1]江苏大学附属人民医院血液科,江苏镇江212002 [2]江苏大学附属人民医院肿瘤科,江苏镇江212002 [3]江苏大学附属人民医院中心实验室,江苏镇江212002

出　　处：《现代肿瘤医学》2024年第21期4148-4153,共6页Journal of Modern Oncology

基　　金：国家自然科学基金(编号:82300164,82270179);江苏省自然科学基金(编号:BK20221287,BK20230296);江苏省卫健委科研项目(编号:M2022123);江苏省镇江市社会发展项目(编号:SH2022027,SH2023009);江苏大学第二十二批学生科研课题立项(编号:Y22A086)。

摘　　要：目的:探索分化抑制因子3及分化抑制因子4(inhibitor of differentiation 3 and inhibitor of differentiation 4,ID3/ID4)两基因在急性髓系白血病(acute myeloid leukemia,AML)患者骨髓中的表达及其临床意义。方法:应用实时荧光定量PCR的方法检测32例非恶性血液病(设对照组)及133例初诊AML患者骨髓单个核细胞中ID3/ID4转录本水平,通过分组分析两者表达的临床意义。结果:AML患者骨髓中ID3/ID4转录本水平较对照组均显著降低(P=0.001及0.002),并且两者之间表达存在轻度正相关(r=0.282,P=0.001)。接收者操作特征曲线分析揭示ID3/ID4转录本水平可作为辅助诊断AML的潜在分子标志(AUC=0.682,P=0.001及AUC=0.673,P=0.002)。通过分组分析发现ID3低表达组患者年龄略小于ID3高表达组患者(P=0.054),NRAS突变频率略低于ID3高表达组患者(P=0.053)。ID4低表达组患者白细胞计数略高于ID4高表达组患者(P=0.088),CEBPA突变频率略高于ID4高表达组患者(P=0.099)。此外,无论在全部患者还是非M3患者中,ID4低表达组病例经过诱导化疗后达完全缓解的概率略低于ID4高表达组病例(P=0.080及0.065)。生存分析发现AML患者及其亚组(非M3及正常核型)中ID3低表达与ID3高表达组患者总体生存相似(P>0.05),ID4低表达病例的总体生存略低于ID4高表达组病例(P=0.058),而在非M3及正常核型患者中存在显著统计学差异(P=0.014及0.002)。结论:ID3/ID4表达下调可能是AML中的常见分子事件,其中ID4表达可能为AML预后判断提供重要参考。Objective:To explore the expression and clinical implication of inhibitor of differentiation 3 and inhibitor of differentiation 4(ID3/ID4)genes in patients with acute myeloid leukemia(AML).Methods:Real-time quantitative PCR was applied to detect the transcript level of ID3/ID4 genes in bone marrow mononuclear cells of 32 non-hematological diseases(control group)and 133 newly diagnosed AML.Clinical implication of ID3/ID4 expression was further analyzed in groups.Results:The transcript level of ID3/ID4 was significantly decreased in AML patients compared with the control group(P=0.001 and 0.002,respectively),and ID3 expression was positively correlated with ID4 expression in AML(r=0.282,P=0.001).Receiver operating characteristic curve demonstrated that ID3/ID4 transcript level may be acted as potential biomarker helpful for the diagnosis of AML(AUC=0.682,P=0.001 and AUC=0.673,P=0.002,respectively).Clinically,patients with low expression of ID3 had a slightly lower age and frequency of NRAS mutation than those with high expression of ID3(P=0.054 and 0.053,respectively).ID4 low-expressed patients tended to have a higher white blood cells and frequency of CEBPA mutation compared with ID4 high-expressed patients(P=0.088 and 0.099,respectively).In addition,patients with low ID4 expression showed a slightly lower complete remission rate than those with high ID4 expression in both total AML(P=0.080)and non-M3 AML(P=0.065)after induction therapy.Survival analysis revealed that patients with low ID3 expression had a similar overall survival compared with patients with high ID3 expression among total AML and other subtypes(non-M3 and cytogenetically normal AML)(P>0.05).However,ID4 low-expressed patients tended to have a lower overall survival than ID4 high-expressed patients(P=0.058),and with statistical significance in non-M3 AML and cytogenetically normal AML(P=0.014 and 0.002,respectively).Conclusion:Reduced ID3/ID4 expression may be common events in AML,and ID4 expression may provide crucial prognostic information.

关 键 词：急性髓系白血病 ID3 ID4 临床意义 

分 类 号：R733[医药卫生—肿瘤]