In:
Blood, American Society of Hematology, Vol. 120, No. 10 ( 2012-09-06), p. 2118-2126
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.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood-2012-02-411827
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2012
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
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