Overexpression of LEF1 predicts unfavorable outcome in adult patients with B-precursor acute lymphoblastic leukemia
Menée sur 282 patients adultes atteints d'une leucémie lymphoblastique aiguë à précurseurs B, cette étude montre qu'une surexpression du gène LEF1 (codant pour un facteur de transcription impliqué dans la voie de signalisation Wnt) est associée à un pronostic défavorable
Aberrant activation of the Wnt pathway plays a pathogenetic role in various tumors and has been associated with adverse outcome in acute lymphoblastic leukemia (ALL). LEF1, a key mediator of Wnt signaling, has been linked to leukemic transformation and recurrent mutations of LEF1 have been identified in pediatric T-ALL. Here, we evaluated the prognostic significance of LEF1 expression in B-precursor ALL patients. LEF1 expression was determined by quantitative real-time RT-PCR in 282 adult B-precursor ALL patients treated on 06/99 and 07/03 GMALL trials. Patients were grouped into quartiles (Q1-4) according to LEF1 expression levels [LEF1 high (Q4; n=71); LEF1 low (Q1-3; n=211)]. Patients with high LEF1 expression had a significantly shorter relapse-free survival (RFS) compared to low LEF1 expressers (5-year RFS: LEF1 high: 27%, LEF1 low: 47%; P=0.05). Importantly, high LEF1 expression was also associated with inferior RFS in standard risk patients and was independently predictive for RFS (P=0.02) in multivariate analyses for this subgroup. Thus, high LEF1 expression identifies B-precursor ALL patients with inferior RFS, supporting a pathogenetic role of Wnt signaling in ALL. Standard risk patients with high LEF1 expression might benefit from early treatment modifications and new molecular therapies including agents targeting the Wnt pathway.
Blood , résumé, 2011