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八聚体结合转录因子4与复杂核型、FLT3-ITD突变及较差的风险分层相关,并预测急性髓系白血病患者的预后不良。

Octamer-binding transcription factor 4 correlates with complex karyotype, FLT3-ITD mutation and poorer risk stratification, and predicts unfavourable prognosis in patients with acute myeloid leukaemia.

作者信息

Xiang Yongsheng, Zhou Xiaofen

机构信息

a Department of Hematology , The First People's Hospital of Jingmen , Jingmen , People's Republic of China.

b Department of Hematology , Xiangyang Central Hospital, The Affiliated Hospital of Hubei University of Arts and Science , Xiangyang , People's Republic of China .

出版信息

Hematology. 2018 Dec;23(10):721-728. doi: 10.1080/10245332.2018.1482050. Epub 2018 Jun 27.

DOI:10.1080/10245332.2018.1482050
PMID:29950146
Abstract

Objective To investigate the correlation of octamer-binding transcription factor 4 (OCT4) expression with clinicopathological features and its predictive value for treatment response as well as survival profiles in de novo acute myeloid leukaemia (AML) patients. Method One hundred fifty-two de novo AML patients and 52 non-hematologic malignancy patients were recruited in this prospective cohort study. OCT4 expression was determined in bone marrow sample collected before treatment. Complete response (CR), event free survival (EFS) and overall survival (OS) were evaluated. Results Compared with the controls, OCT4 mRNA expression was higher in AML patients (P < .001), and higher OCT4 expression was correlated with presence of complex karyotype (CK) (P = .037), FLT3-ITD mutation (P = .012) and poorer risk stratification (P < .001) in AML patients. As to predictive value, OCT4 mRNA expression was decreased in patients achieved CR compared to non-CR patients (P = .022). Kaplan-Meier (K-M) curves showed that shorter EFS (9.0 (95% CI (7.7-10.3)) months vs. 25.0 (95% CI (17.5-32.5)) months, P < .001) and shorter OS (20.0 (95% CI (17.8-22.2) months vs. 33.0 months, P < .001) were observed in OCT4 mRNA high expression patients compared to OCT4 mRNA low expression patients. Multivariate Cox's proportional hazards regression analyses revealed that OCT4 mRNA high expression was an independent predictive factor for shorter EFS and OS in AML patients. Conclusion OCT4 correlates with presence of CK, FLT3-ITD mutation and poorer risk stratification, and it could be served as a convincing biomarker for predicting unfavourable prognosis in AML patients.

摘要

目的 探讨八聚体结合转录因子4(OCT4)表达与初发急性髓系白血病(AML)患者临床病理特征的相关性及其对治疗反应和生存情况的预测价值。方法 本前瞻性队列研究纳入了152例初发AML患者和52例非血液系统恶性肿瘤患者。在治疗前采集的骨髓样本中测定OCT4表达。评估完全缓解(CR)、无事件生存期(EFS)和总生存期(OS)。结果 与对照组相比,AML患者的OCT4 mRNA表达更高(P < 0.001),且OCT4表达升高与AML患者复杂核型(CK)的存在(P = 0.037)、FLT3-ITD突变(P = 0.012)及较差的危险分层(P < 0.001)相关。关于预测价值,与未达到CR的患者相比,达到CR的患者OCT4 mRNA表达降低(P = 0.022)。Kaplan-Meier(K-M)曲线显示,与OCT4 mRNA低表达患者相比,OCT4 mRNA高表达患者的EFS较短(9.0(95%CI(7.7 - 10.3))个月对25.0(95%CI(17.5 - 32.5))个月,P < 0.001),OS也较短(20.0(95%CI(17.8 - 22.2))个月对33.0个月,P < 0.001)。多变量Cox比例风险回归分析显示,OCT4 mRNA高表达是AML患者EFS和OS较短的独立预测因素。结论 OCT4与CK的存在、FLT3-ITD突变及较差的危险分层相关,可作为预测AML患者不良预后的可靠生物标志物。

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