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

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: MKlow group and MKhigh group.Results: MKhigh patients had higher white blood cell counts, higher peripheral blood blasts percentages, and higher minimal residual disease levels than MKlow patients. Moreover, the MK gene was expressed significantly higher in patients with relapsed ALL than in patients who maintained complete remission or at diagnosis. MKhigh patients harbored inferior relapse-free survival (RFS, P = 0.047) and overall survival (OS, P = 0.022) than MKlow 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.

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。患者以中位值进行二分，并分为两组：MK低表达组和MK高表达组。 结果：MK高表达患者的白细胞计数、外周血原始细胞百分比以及微小残留病水平均高于MK低表达患者。此外，复发ALL患者的MK基因表达明显高于维持完全缓解或初诊时的患者。MK高表达患者的无复发生存期（RFS，P = 0.047）和总生存期（OS，P = 0.022）均低于MK低表达患者，并且在整个队列中发现MK高表达是总生存期较差的独立预测因素（P = 0.032），但不是无复发生存期的独立预测因素（P = 0.077）。 结论与讨论：MK高表达是儿童ALL的一个独立不良预后因素。其水平可纳入改进的ALL风险分类系统，并提示需要替代治疗方案。