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Constitutive activation of the Wnt/β-catenin signalling pathway in acute myeloid leukaemia

Oncogene volume 24, pages 2410–2420 (2005)Cite this article

Abstract

The β-catenin protein is at the core of the canonical Wnt signalling pathway. Wnt stimulation leads to β-catenin accumulation, nuclear translocation and interaction with T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors to regulate genes important for embryonic development and proliferation. Wnt/β-catenin can promote stem cell self-renewal and is dysregulated in colon carcinoma. We have examined the role of the Wnt pathway in the development of acute myeloid leukaemia (AML) and find that the β-catenin protein is readily detected in primary AML samples. Using transfection of a TCF/LEF reporter construct into primary AML cells and normal human progenitors, we find increased reporter activity in 16/25 leukaemia samples. Retrovirally mediated expression of a mutant active β-catenin in normal progenitors preserves CD34 expression and impairs myelomonocytic differentiation. Activation of TCF/LEF signalling decreases factor withdrawal-induced apoptosis of normal progenitors. A significant proportion of AML cases show aberrant expression of components of the Wnt pathway including Wnt-1, Wnt-2b and LEF-1. These results provide evidence for the involvement of the Wnt/β-catenin pathway in the pathogenesis of AML.

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Acknowledgements

MS was supported by Leukaemia Research, UK, VLG by the Kay Kendall Leukaemia Fund and AK by the Medical Research Council, UK.

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  1. Department of Haematology, Royal Free & University College Medical School, 98 Chenies Mews, London, WC1E 6HX, UK

    Maria Simon, Victoria L Grandage, David C Linch & Asim Khwaja

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  1. Maria Simon
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  2. Victoria L Grandage
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  3. David C Linch
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Correspondence to Asim Khwaja.

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Simon, M., Grandage, V., Linch, D. et al. Constitutive activation of the Wnt/β-catenin signalling pathway in acute myeloid leukaemia. Oncogene 24, 2410–2420 (2005). https://doi.org/10.1038/sj.onc.1208431

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