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Type: Journal article
Title: Osteoclasts control reactivation of dormant myeloma cells by remodelling the endosteal niche
Author: Lawson, M.
McDonald, M.
Kovacic, N.
Khoo, W.
Terry, R.
Down, J.
Kaplan, W.
Paton-Hough, J.
Fellows, C.
Pettitt, J.
Dear, T.
Van Valckenborgh, E.
Baldock, P.
Rogers, M.
Eaton, C.
Vanderkerken, K.
Pettit, A.
Quinn, J.
Zannettino, A.
Phan, T.
et al.
Citation: Nature Communications, 2015; 6(1):8986-1-8986-15
Publisher: Nature Publishing Group
Issue Date: 2015
ISSN: 2041-1723
Statement of
Michelle A. Lawson, Michelle M. McDonald, Natasa Kovacic, Weng Hua Khoo, Rachael L. Terry, Jenny Down, Warren Kaplan, Julia Paton-Hough, Clair Fellows, Jessica A. Pettitt, T. Neil Dear, Els Van Valckenborgh, Paul A. Baldock, Michael J. Rogers, Colby L. Eaton, Karin Vanderkerken, Allison R. Pettit, Julian M.W. Quinn, Andrew C.W. Zannettino, Tri Giang Phan, Peter I. Croucher
Abstract: Multiple myeloma is largely incurable, despite development of therapies that target myeloma cell-intrinsic pathways. Disease relapse is thought to originate from dormant myeloma cells, localized in specialized niches, which resist therapy and repopulate the tumour. However, little is known about the niche, and how it exerts cell-extrinsic control over myeloma cell dormancy and reactivation. In this study, we track individual myeloma cells by intravital imaging as they colonize the endosteal niche, enter a dormant state and subsequently become activated to form colonies. We demonstrate that dormancy is a reversible state that is switched 'on' by engagement with bone-lining cells or osteoblasts, and switched 'off' by osteoclasts remodelling the endosteal niche. Dormant myeloma cells are resistant to chemotherapy that targets dividing cells. The demonstration that the endosteal niche is pivotal in controlling myeloma cell dormancy highlights the potential for targeting cell-extrinsic mechanisms to overcome cell-intrinsic drug resistance and prevent disease relapse.
Keywords: Osteoclasts; myeloma; endosteal niche
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.To view a copy of this license, visit
DOI: 10.1038/ncomms9983
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