title: High expression of lymphoid enhancer-binding factor-1 (LEF1) is a novel favorable prognostic factor in cytogenetically normal acute myeloid leukemia.
abstract: 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 (LEF1high) 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, LEF1high 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, 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 up-regulation 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.
authors: Department of Internal Medicine III and Laboratory for Leukemia Diagnostics, Ludwig-Maximilians-Universität, Munich, Germany.
authors: Klaus H
authors: KH
authors: Metzeler
authors: Bernhard
authors: B
authors: Heilmeier
authors: Katrin E
authors: KE
authors: Edmaier
authors: Vijay P S
authors: VP
authors: Rawat
authors: Annika
authors: A
authors: Dufour
authors: Konstanze
authors: K
authors: Döhner
authors: Michaela
authors: M
authors: Feuring-Buske
authors: Jan
authors: J
authors: Braess
authors: Karsten
authors: K
authors: Spiekermann
authors: Thomas
authors: T
authors: Büchner
authors: Maria C
authors: MC
authors: Sauerland
authors: Hartmut
authors: H
authors: Döhner
authors: Wolfgang
authors: W
authors: Hiddemann
authors: Stefan K
authors: SK
authors: Bohlander
authors: Richard F
authors: RF
authors: Schlenk
authors: Lars
authors: L
authors: Bullinger
authors: Christian
authors: C
authors: Buske
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016019:Survival Analysis; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1