High expression of lymphoid enhancer-binding factor-1 (LEF1) is a novel favorable prognostic factor in cytogenetically normal acute myeloid leukemia
High expression of lymphoid enhancer-binding factor-1 (LEF1) is a novel favorable prognostic factor in cytogenetically normal acute myeloid leukemia
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DOI：
10.1182/blood-2012-02-411827
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发表时间：
2012-09-06
期刊：
影响因子：
20.3
通讯作者：
Buske, Christian
中科院分区：
文献类型：
--
作者：
Metzeler, Klaus H.;Heilmeier, Bernhard;Buske, Christian
淋巴增强因子结合因子-1 （LEF1）是Wnt信号的关键转录因子。我们最近在小鼠中发现了异常的LEF1表达诱导急性髓性白血病（AML），并在细胞遗传学正常的AML （CN-AML）患者中发现了高表达的LEF1。LEF1表达是否与患者的临床和分子特征以及治疗结果相关尚不清楚。因此，我们在德国AML合作组试验中使用微阵列研究了210名CN-AML成人患者的LEF1表达。LEF1高表达（LEF1(High)）与更好的无复发生存期（RFS, P < 0.001）、总生存期（OS, P < 0.001）和无事件生存期（EFS, P < 0.001）相关。在多变量分析中调整已建立的预后因子，LEF1（高）状态仍然与延长的RFS （P = 0.007）、OS （P = 0.01）和EFS （P = 0.003）相关。在由德国-奥地利AML研究组提供的196例CN-AML患者的独立验证队列中，LEF1（高）患者的OS （P = 0.02）和EFS （P = 0.04）显着延长。我们通过定量PCR验证了LEF1表达与预后的相关性，从而为将该标志物纳入未来CN-AML风险分层系统提供了一个临床应用平台。基因表达谱和免疫表型分析显示，在LEF1（高）患者中，淋巴细胞相关基因和淋巴样细胞表面抗原上调。总之，我们提供的证据表明，高LEF1表达是CN-AML的一个新的有利预后标志物。[血液杂志];2012;120(10):2118-2126]
Lymphoid enhancer-binding factor-1 (LEF1) is a key transcription factor of Wnt signaling. We recently showed that aberrant LEF1 expression induces acute myeloid leukemia (AML) in mice, and found high LEF1 expression in a subset of cytogenetically normal AML (CN-AML) patients. Whether LEF1 expression associates with clinical and molecular patient characteristics and treatment outcomes remained unknown. We therefore studied LEF1 expression in 210 adults with CN-AML treated on German AML Cooperative Group trials using microarrays. High LEF1 expression (LEF1(high)) associated with significantly better relapse-free survival (RFS; P < .001), overall survival (OS; P < .001), and event-free survival (EFS; P < .001). In multivariable analyses adjusting for established prognosticators, LEF1(high) status remained associated with prolonged RFS (P = .007), OS (P = .01), and EFS (P = .003). In an independent validation cohort of 196 CN-AML patients provided by the German-Austrian AML Study Group, LEF1(high) patients had significantly longer OS (P = .02) and EFS (P = .04). We validated the prognostic relevance of LEF1 expression by quantitative PCR, thereby providing a clinically applicable platform to incorporate this marker into future risk-stratification systems for CN-AML. Gene-expression profiling and immunophenotyping revealed up-regulation of lymphopoiesis-related genes and lymphoid cell-surface antigens in LEF1(high) patients. In summary, we provide evidence that high LEF1 expression is a novel favorable prognostic marker in CN-AML. (Blood. 2012; 120(10):2118-2126)