High expression of lymphoid enhancer-binding factor-1 (LEF1) is a novel favorable prognostic factor in cytogenetically normal acute myeloid leukemia
Menée sur 210 patients allemands atteints d'une leucémie myéloïde aiguë sans anomalie cytogénétique, cette étude évalue l'association entre l'expression du facteur LEF-1 et le pronostic de la maladie
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 (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 (LEF1high) associated with significantly better relapse-free (RFS; P<.001), overall (OS; P<.001) and event-free (EFS; P<.001) survival. In multivariable analyses adjusting for established prognosticators, LEF1high status remained associated with prolonged RFS (P=.007), OS (P=.01) and EFS (P=.002). In an independent validation cohort of 196 CN-AML patients provided by the German-Austrian AML Study Group, LEF1high 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 upregulation of lymphopoiesis-related genes and lymphoid cell surface antigens in LEF1high patients. In summary, we provide evidence that high LEF1 expression is a novel favorable prognostic marker in CN-AML.
Blood , résumé, 2012