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Acute Leukemias

Expression of β-catenin by acute myeloid leukemia cells predicts enhanced clonogenic capacities and poor prognosis

Leukemia volume 20, pages 1211–1216 (2006)Cite this article

Abstract

Activation of the Wnt/β-catenin pathway has recently been shown to be crucial to the establishment of leukemic stem cells in chronic myeloid leukemia. We sought to determine whether β-catenin was correlated to clonogenic capacity also in the acute myeloid leukemia (AML) setting. Eighty-two patients were retrospectively evaluated for β-catenin expression by Western blot. β-Catenin was expressed (although at various protein levels) in 61% of patients, and was undetectable in the remaining cases. In our cohort, β-catenin expression was correlated with the clonogenic proliferation of AML-colony forming cells (AML-CFC or CFU-L) in methylcellulose in the presence of 5637-conditioned medium, and more strikingly with self-renewing of leukemic cells, as assessed in vitro by a re-plating assay. In survival analyses, β-catenin appeared as a new independent prognostic factor predicting poor event-free survival and shortened overall survival (both with P<0.05). Furthermore, variations in β-catenin protein levels were dependent on post-transcriptional mechanisms involving the Wnt/β-catenin pathway only in leukemic cells. Indeed, β-catenin negative leukemic cells were found to increase β-catenin in response to Wnt3a agonist in contrast to normal counterparts. Altogether, our data pave the way to the evaluation of Wnt pathway inhibition as a new rationale for eradicating the clonogenic pool of AML cells.

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Acknowledgements

Research grants and financial support: LY is supported by a grant from the Fondation de France-Fédération Nationale des Centres de Lutte Contre le Cancer. This work was supported by a grant from the Association de Recherche contre le Cancer (contract 3638).

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Authors and Affiliations

  1. Département Oncogenèse et Signalisation dans les cellules Hématopoïétiques, INSERM U563, Centre de Physiopathologie Toulouse Purpan (CPTP), CHU Purpan, Toulouse Cedex, France

    L Ysebaert, G Chicanne, C Demur, F De Toni, N Prade-Houdellier, V Mansat-De Mas, G Laurent, B Payrastre, S Manenti & C Racaud-Sultan

  2. Service d'Hématologie clinique, CHU Purpan, Toulouse, France

    L Ysebaert, F Rigal-Huguet & G Laurent

  3. Service d'Hématologie biologique, CHU Purpan, Toulouse, France

    C Demur & V Mansat-De Mas

  4. INSERM U558, Faculté de Médecine de Toulouse, Toulouse, France

    J-B Ruidavets

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  1. L Ysebaert
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Correspondence to L Ysebaert.

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Ysebaert, L., Chicanne, G., Demur, C. et al. Expression of β-catenin by acute myeloid leukemia cells predicts enhanced clonogenic capacities and poor prognosis. Leukemia 20, 1211–1216 (2006). https://doi.org/10.1038/sj.leu.2404239

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