Albano Francesco, Zagaria Antonella, Anelli Luisa, Orsini Paola, Minervini Crescenzio Francesco, Impera Luciana, Casieri Paola, Coccaro Nicoletta, Tota Giuseppina, Brunetti Claudia, Minervini Angela, Pastore Domenico, Carluccio Paola, Mestice Anna, Cellamare Angelo, Specchia Giorgina
Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari, Bari, Italy.
Oncotarget. 2014 Feb 15;5(3):649-58. doi: 10.18632/oncotarget.1619.
Lymphoid enhancer-binding factor 1 (LEF1) is a downstream effector of the Wnt/ β-catenin signaling pathway. High LEF1 expression has been reported as a prognostic marker in hematologic malignancies. We evaluated the prognostic significance of LEF1 expression in 78 adult acute promyelocytic leukemia (APL) patients. APL samples were dichotomized at the median value and divided into: LEF1(low) and LEF1(high). LEF1(high) patients had lower WBC counts at baseline and were less likely to carry a FLT3-ITD than LEF1(low) patients. Early death occurred only in the LEF1(low) group. Moreover, LEF1(low) expression was associated with a high Sanz score. Survival analysis of 61 APL patients < 60 years revealed that the LEF1(high) group had a significantly longer overall survival (OS). Cox analysis for OS confirmed only LEF1 expression as an independent prognostic factor. Of the 17 patients over the age of 60, those in the LEF1(high) group showed a higher median survival. In silico analysis identified 9 differentially expressed, up-modulated genes associated with a high expression of LEF1; the majority of these genes is involved in the regulation of apoptosis. Our study provides evidence that LEF1 expression is an independent prognostic factor in APL, and could be used in patients risk stratification.
淋巴细胞增强因子1(LEF1)是Wnt/β-连环蛋白信号通路的下游效应分子。已有报道称LEF1高表达是血液系统恶性肿瘤的一个预后标志物。我们评估了78例成人急性早幼粒细胞白血病(APL)患者中LEF1表达的预后意义。APL样本按中位数进行二分法划分,分为:LEF1(低)组和LEF1(高)组。LEF1(高)组患者基线时白细胞计数较低,携带FLT3-ITD的可能性低于LEF1(低)组患者。早期死亡仅发生在LEF1(低)组。此外,LEF1(低)表达与高Sanz评分相关。对61例年龄<60岁的APL患者进行生存分析发现,LEF1(高)组的总生存期(OS)显著更长。对OS进行Cox分析证实只有LEF1表达是一个独立的预后因素。在17例年龄超过60岁的患者中,LEF1(高)组患者的中位生存期更高。计算机分析确定了9个与LEF1高表达相关的差异表达上调基因;这些基因中的大多数参与细胞凋亡的调控。我们的研究提供了证据表明LEF1表达是APL中的一个独立预后因素,可用于患者的风险分层。