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中期因子(MK)的高表达表明儿童急性淋巴细胞白血病预后不良。

High expression of Midkine (MK) indicates poor prognosis in childhood acute lymphoblastic leukemia.

作者信息

Jia Ming, Zhao Hai-Zhao, Cheng Yu-Ping, Luo Ze-Bin, Zhang Jing-Ying, Li Si-Si, Xu Xiao-Jun, Tang Yong-Min

机构信息

a Division of Hematology-Oncology , Children's Hospital of Zhejiang University School of Medicine, Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education , Hangzhou 310003 , PR China.

出版信息

Hematology. 2016 Mar;21(2):69-77. doi: 10.1179/1607845415Y.0000000050. Epub 2015 Sep 9.

Abstract

OBJECTIVES

Midkine (MK) expression has been reported to be correlated with the poor prognosis of patients with various tumors. However, there are no data available about the prognostic value of MK expression in childhood acute lymphoblastic leukemia (ALL).

METHODS

In this study, MK mRNA expression was determined by real-time polymerase chain reaction in 120 childhood ALL and 30 healthy volunteers. Patients were dichotomized at the median value and divided into two groups: MK(low) group and MK(high) group.

RESULTS

MK(high) patients had higher white blood cell counts, higher peripheral blood blasts percentages, and higher minimal residual disease levels than MK(low) patients. Moreover, the MK gene was expressed significantly higher in patients with relapsed ALL than in patients who maintained complete remission or at diagnosis. MK(high) patients harbored inferior relapse-free survival (RFS, P = 0.047) and overall survival (OS, P = 0.022) than MK(low) patients, and high expression of MK was found to be independently predictive of inferior OS (P = 0.032) but not RFS (P = 0.077) in the overall cohort.

CONCLUSION AND DISCUSSION

MK high expression is an independent adverse prognostic factor in childhood ALL. Its level may be incorporated into an improved risk classification system for ALL and suggest the need of alternative regimens.

摘要

目的

据报道,中期因子(MK)的表达与多种肿瘤患者的不良预后相关。然而,关于MK表达在儿童急性淋巴细胞白血病(ALL)中的预后价值尚无相关数据。

方法

在本研究中,通过实时聚合酶链反应测定了120例儿童ALL患者和30名健康志愿者的MK mRNA表达。患者按中位数进行二分法分组,分为两组:MK(低)组和MK(高)组。

结果

与MK(低)组患者相比,MK(高)组患者的白细胞计数更高、外周血原始细胞百分比更高、微小残留病水平更高。此外,复发ALL患者的MK基因表达明显高于维持完全缓解或诊断时的患者。与MK(低)组患者相比,MK(高)组患者的无复发生存期(RFS,P = 0.047)和总生存期(OS,P = 0.022)较差,并且在整个队列中发现MK的高表达是OS较差(P = 0.032)的独立预测因素,但不是RFS(P = 0.077)的独立预测因素。

结论与讨论

MK高表达是儿童ALL的独立不良预后因素。其水平可纳入改进的ALL风险分类系统,并提示需要替代方案。

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