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      Activation of Wnt/beta-catenin pathway mediates growth and survival in B-cell progenitor acute lymphoblastic leukaemia.

      British Journal of Haematology

      Adolescent, Adult, Apoptosis, genetics, Blotting, Western, methods, Burkitt Lymphoma, metabolism, pathology, Cell Cycle Proteins, Child, Child, Preschool, Female, Flow Cytometry, Fluorescent Antibody Technique, Gene Expression Profiling, Gene Expression Regulation, Leukemic, Humans, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Signal Transduction, physiology, Tumor Cells, Cultured, Wnt Proteins, Wnt3 Protein, Wnt3A Protein, beta Catenin

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          Abstract

          This study investigated the response of acute lymphoblastic leukaemia (ALL) cells to Wnt proteins. Accumulation of beta-catenin was measured by Western blotting and immunofluorescence microscopy. Reverse transcription polymerase chain reaction (RT-PCR) analysis of B-cell progenitor acute lymphoblastic leukaemia (ALL) cells revealed expression of Wnt genes, including WNT2B in 33%, WNT5A in 42%, WNT10B in 58% and WNT16B in 25% of cases. The Wnt receptors, (Frizzled) FZD7 and FZD8 were also expressed in most cases while FZD3, FZD4 and FZD9 were occasionally detected. Stimulation of ALL cells with Wnt-3a activated canonical Wnt signalling with increased expression and nuclear translocation of beta-catenin. This resulted in a 1.7- to 5.3-fold increase in cell proliferation, which was associated with enhanced cell cycle entry. A significant increase in the survival of ALL cells under conditions of serum deprivation was also observed. Microarray analysis and quantitative RT-PCR revealed that activation of the Wnt/beta-catenin pathway led to altered expression of genes involved in cell cycle regulation and apoptosis in normal and leukaemic B-cell progenitors. Our results demonstrate that Wnt-3a provides proliferative and survival cues in ALL cells. This data suggests that targeting the Wnt signalling pathway may be a useful therapeutic strategy in ALL.

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          Author and article information

          Journal
          17614820
          10.1111/j.1365-2141.2007.06667.x

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