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Metzeler, K.H.* ; Heilmeier, B.* ; Edmaier, K.E.* ; Rawat, V.P.S.* ; Dufour, A.* ; Döhner, K.* ; Feuring-Buske, M.* ; Braess, J. ; Spiekermann, K. ; Büchner, T.* ; Sauerland, M.C.* ; Döhner, H.* ; Hiddemann, W. ; Bohlander, S.K. ; Schlenk, R.F.* ; Bullinger, L.* ; Buske, C.*

High expression of Lymphoid Enhancer-binding Factor-1 (LEF1) is a novel favorable prognostic factor in cytogenetically normal acute myeloid leukemia.

Blood 120, 2118-2126 (2012)
Open Access Green as soon as Postprint is submitted to ZB.
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)
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Publication type Article: Journal article
Document type Scientific Article
Keywords Acute Lymphoblastic-Leukemia; Stem-Cell Transplantation; High-Dose Cytarabine; Normal Karyotype AMLl; Gene-Expression; Myelodysplastic Syndromes; Translocation Products; Prolonged Maintenance; Signaling Pathway; Adult Patients
ISSN (print) / ISBN 0006-4971
e-ISSN 1528-0020
Journal Blood
Quellenangaben Volume: 120, Issue: 10, Pages: 2118-2126 Article Number: , Supplement: ,
Publisher American Society of Hematology
Reviewing status Peer reviewed