Overexpression of lymphoid enhancer-binding factor-1 (LEF1) is a novel favorable prognostic factor in childhood acute lymphoblastic leukemia

Overexpression of lymphoid enhancer-binding factor-1 (LEF1) is a novel favorable prognostic factor in childhood acute lymphoblastic leukemia
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淋巴增强子结合因子-1 (LEF1) 的过度表达是儿童急性淋巴细胞白血病的新型有利预后因素

DOI:
10.1111/ijlh.12375
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发表时间:
2015-10-01
影响因子:
3
通讯作者:
Tang, Y-M
Tang, Y-M
中科院分区:
医学4区
文献类型:
--
作者:
Jia, M.;Zhao, H-Z;Tang, Y-M

文献摘要

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前言:淋巴增强因子-1(LEF1)是Wnt信号通路的靶基因和中枢调节因子。LEF1的高表达可作为判断成人多种恶性血液病患者预后的指标。方法:采用实时定量聚合酶链式反应技术检测12 2例初诊ALL患儿中LEF1的表达情况。结果:ALL患者LEF1基因表达水平明显高于正常对照组,诱导治疗后LEF1基因表达水平明显下降。此外,与LEF1低的患者相比,LEF1高的患者在确诊时的白细胞(WBC)计数和完全缓解时的微小残留病(MRD)水平都低于LEF1低的患者。最后,我们的研究表明,LEF1的高表达与良好的CR率和儿童ALL的总生存率(5年OS:LEF1(高)92%对LEF1(低)73%,P=0.009)相关。在bcr-abl阴性ALL患者亚组中,高水平的LEF1水平与良好的无复发生存率相关,也与较好的OS相关。结论:LEF1的过度表达是儿童ALL预后的有利因素。LEF1的预后影响可能有助于治疗分层,并建议需要替代方案。
Introduction: Lymphoid enhancer-binding factor-1 (LEF1) is a target gene and central mediator of the Wnt signaling pathway. High LEF1 expression has been reported as a prognostic marker in several types of hematologic malignancies of adult patients.Methods: In this study, LEF1 expression was analyzed by real-time polymerase chain reaction (PCR) in 122 children with newly diagnosed ALL treated on the China NPCAC97 protocols. Patients' samples were dichotomized at the median value of control group and divided into LEF1(low) and LEF1(high) groups.Results: The LEF1 mRNA levels in patients with ALL were significantly higher than those of normal controls, and the LEF1 levels were dramatically decreased following induction therapy. In addition, LEF1 high patients had lower white blood cell (WBC) count at diagnosis and lower minimal residual disease (MRD) levels at the time of complete remission as compared to LEF1 low patients. Finally, our studies showed that high LEF1 expression is associated with favorable CR rate and overall survival (OS) in childhood ALL (5-year OS: LEF1(high) 92% vs. LEF1(low) 73%, P = 0.009). High LEF1 level was associated with a favorable relapse-free survival in standard- risk patients and also related to a better OS within the subgroup of patients with BCR-ABL-negative ALL.Conclusion: Overexpression of LEF1 is a favorable prognostic factor in childhood ALL. The prognostic impact of LEF1 may assist treatment stratification and suggest the need of alternative regimens.