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LEF-1 drives aberrant β-catenin nuclear localization in myeloid leukemia cells

Morgan, Rhys G.; Ridsdale, Jenna; Payne, Megan; Heesom, Kate J.; Wilson, Marieangela C.; Davidson, Andrew D.; Greenhough, Alexander; Davies, Sara; Williams, Ann C.; Blair, Allison; Waterman, Marian L.; Tonks, Alex; Darley, Richard L.

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Rhys G. Morgan

Jenna Ridsdale

Megan Payne

Kate J. Heesom

Marieangela C. Wilson

Andrew D. Davidson

Sara Davies

Ann C. Williams

Allison Blair

Marian L. Waterman

Alex Tonks

Richard L. Darley


Canonical Wnt/β-catenin signaling is frequently dysregulated in myeloid leukemias and is implicated in leukemogenesis. Nuclear-localized β-catenin is indicative of active Wnt signaling and is frequently observed in acute myeloid leukemia patients; however, some patients exhibit little or no nuclear β-catenin even where cytosolic β-catenin is abundant. Control of the subcellular localization of β-catenin therefore represents an additional mechanism regulating Wnt signaling in hematopoietic cells. To investigate the factors mediating the nuclear-localization of β-catenin we carried out the first nuclear/cytoplasmic proteomic analysis of the β-catenin interactome in myeloid leukemia cells and identified putative novel β-catenin interactors. Comparison of interacting factors between Wnt-responsive cells (high nuclear β-catenin) versus Wnt-unresponsive cells (low nuclear β-catenin) suggested the transcriptional partner, LEF-1, could direct the nuclear-localization of β-catenin. The relative levels of nuclear LEF-1 and β-catenin were tightly correlated in both cell lines and in primary AML blasts. Furthermore, LEF-1 knockdown perturbed β-catenin nuclear-localization and transcriptional activation in Wnt-responsive cells. Conversely, LEF-1 overexpression was able to promote both nuclear-localization and β-catenin-dependent transcriptional responses in previously Wnt-unresponsive cells. This is the first β-catenin interactome study in hematopoietic cells and reveals LEF-1 as a mediator of nuclear β-catenin level human myeloid leukemia.


Morgan, R. G., Ridsdale, J., Payne, M., Heesom, K. J., Wilson, M. C., Davidson, A. D., …Darley, R. L. (2019). LEF-1 drives aberrant β-catenin nuclear localization in myeloid leukemia cells. Haematologica, 104(7), 1365-1377.

Journal Article Type Article
Acceptance Date Jan 3, 2019
Online Publication Date Jan 10, 2019
Publication Date Jun 30, 2019
Deposit Date Feb 12, 2019
Publicly Available Date Feb 18, 2019
Journal Haematologica
Print ISSN 0390-6078
Electronic ISSN 1592-8721
Publisher Ferrata Storti Foundation
Peer Reviewed Peer Reviewed
Volume 104
Issue 7
Pages 1365-1377
Keywords acute myeloid leukemia, B-Catenin, LEF-1, Signal transduction, WNT signaling
Public URL
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