High LEF1 expression predicts adverse prognosis in chronic lymphocytic leukemia and may be targeted by ethacrynic acid

• DOI: 10.18632/oncotarget.7795
• Publication Date: 2016-03-01T03:32:25Z
• Authors: Wei Wu; Huayuan Zhu; Yuan Fu; Wenyi Shen; Kourong Miao; Min Hong; Wei Xu; Lei Fan; Ken H. Young; Peng Liu; Jianyong Li
• Keywords: Adult; Aged, 80 and over; Male; 0301 basic medicine; Gene Expression Regulation, Leukemic; Lymphoid Enhancer-Binding Factor 1; Apoptosis; Middle Aged; Prognosis; Leukemia, Lymphocytic, Chronic, B-Cell; Survival Analysis; Deubiquitinating Enzyme CYLD; 3. Good health; Necrosis; Young Adult; 03 medical and health sciences; Ethacrynic Acid; Tumor Cells, Cultured; Humans; Female; RNA Interference; Research Paper; Aged

Aberrant activation of lymphoid enhancer-binding factor-1 (LEF1) has been identified in several cancers, including chronic lymphocytic leukemia (CLL). As a key transcription factor the Wnt/β-catenin pathway, LEF1 helps to regulate important genes involved tumor cell death mechanisms. In this study, we determined gene expression levels CLL (n = 197) and monoclonal B-cell lymphocytosis (MBL) 6) patients through real-time RT-PCR. was significantly up-regulated both MBL compared with normal B cells. Treatment-free survival (TFS) time overall (OS) were much longer low than those high levels. Furthermore, Wnt inhibitor ethacrynic acid (EA) induced apoptosis necroptosis primary EA also enhanced cytotoxicity fludarabine cyclophosphamide against cells vitro. Finally, demonstrated that functions by inhibiting recruitment DNA promoters restoring cylindromatosis (CYLD) Our results showed, for first time, is associated poor patients. Combined other chemotherapeutic drugs, may be promising therapeutic agent CLL.