title: Clinical significance of lymphoid enhancer-binding factor 1 expression in acute myeloid leukemia.
abstract: Lymphoid enhancer-binding factor 1 (LEF1) is a downstream effector of the Wnt/β-catenin signaling pathway and its dysregulation is associated with a number of malignant diseases such as leukemia. We explored the expression profile of LEF1 in acute myeloid leukemia (AML) and determined its specific prognostic significance in this disease. The LEF1 mRNA level in patients with previously untreated AML was significantly higher than in normal controls. Patients with AML with relatively higher LEF1 expression were more likely to achieve a complete remission (CR) following induction therapy in comparison to those with a lower LEF1 level. Moreover, we provide the first evidence that primary AML samples with AML1-ETO or PML-RARα have a higher LEF1 level compared with those without each fusion gene. High LEF1 expression predicts a significantly better overall survival for patients with intermediate-risk cytogenetics. High LEF1 level was associated with a favorable relapse-free survival in patients with FLT3-ITD wild-type. Finally, a scoring system based on LEF1 level and mutation status of FLT3-ITD or NPM1 is reliable to predict the outcome for AML with intermediate-risk cytogenetics. Our results indicate that LEF1 contributes to the pathophysiology of AML and could serve as a novel predictor of better treatment response. LEF1 level may be incorporated into an improved risk classification system for certain specific subtypes of AML.
authors.affiliation: Department of Hematology.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Fu
authors.forename: Huayuan
authors.initials: H
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Jiadai
authors.initials: J
authors.lastname: Xu
authors.forename: Tingmei
authors.initials: T
authors.lastname: Chen
authors.forename: Bei
authors.initials: B
authors.lastname: Xu
authors.forename: Sixuan
authors.initials: S
authors.lastname: Qian
authors.forename: Jianyong
authors.initials: J
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011379:Prognosis; D000075142:RUNX1 Translocation Partner 1 Protein; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3