Abstract
Lymphoid enhancer-binding factor 1 (LEF1) is a downstream effector of the Wnt/ β-catenin signaling pathway. High LEF1 expression has been reported as a prognostic marker in hematologic malignancies. We evaluated the prognostic significance of LEF1 expression in 78 adult acute promyelocytic leukemia (APL) patients. APL samples were dichotomized at the median value and divided into: LEF1(low) and LEF1(high). LEF1(high) patients had lower WBC counts at baseline and were less likely to carry a FLT3-ITD than LEF1(low) patients. Early death occurred only in the LEF1(low) group. Moreover, LEF1(low) expression was associated with a high Sanz score. Survival analysis of 61 APL patients < 60 years revealed that the LEF1(high) group had a significantly longer overall survival (OS). Cox analysis for OS confirmed only LEF1 expression as an independent prognostic factor. Of the 17 patients over the age of 60, those in the LEF1(high) group showed a higher median survival. In silico analysis identified 9 differentially expressed, up-modulated genes associated with a high expression of LEF1; the majority of these genes is involved in the regulation of apoptosis. Our study provides evidence that LEF1 expression is an independent prognostic factor in APL, and could be used in patients risk stratification.
Highlights
Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) accounting for about 5% of all cases
The association of LEF1high status with a longer overall survival (OS) was confirmed in multivariate analyses adjusting for the most important prognostic factors in APL, such as age, FLT3 status and Sanz score
This fact indicates that Lymphoid enhancer-binding factor 1 (LEF1) gene expression analysis is capable of discriminating APL patients with a poor outcome
Summary
Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) accounting for about 5% of all cases. APL is characterized by abnormal promyelocytes infiltrating bone marrow and other hematopoietic organs, and t(15;17) translocation leading to PML-RARα fusion gene [1]. Induction treatment of APL combining all-trans retinoic acid (ATRA) with anthracycline-based chemotherapy induces a complete remission rate of 90–95% and a cure rate of more than 80% [2,3]. The current riskstratification system for APL is based only on the whitecell and platelet count [4], these parameters could not be confirmed in the German AMLCG trial for younger patients [5]. New molecular biomarkers may help to make a better risk stratification of APL patients and to identify those with a poorer prognosis
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