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Impaired osteogenic differentiation of mesenchymal stem cells derived from multiple myeloma patients is associated with a blockade in the deactivation of the Notch signaling pathway

Leukemia volume 26, pages 2546–2549 (2012)Cite this article

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Multiple myeloma (MM) is a malignant B-cell disorder characterized by the accumulation of neoplastic plasma cells in the bone marrow (BM). One of the major characteristics of MM is the occurrence of bone lesions, caused by an imbalance between osteoblastic and osteoclastic function. Mesenchymal stem cells (MSCs) are a population of multipotent stem cells, which have the potential to differentiate into different mesenchymal tissues. Several previous studies indicated that BM-derived MSCs from MM patients showed an enhanced production of cytokines and a distinctive gene expression profile, as compared with their normal counterparts.1, 2, 3, 4 Although osteoblastic function is decreased in advanced MM, regarding whether and at which level the differentiation of MSCs towards osteoblasts is impaired in this disease, the reports are not unanimous.1, 2, 3

Nowadays, it is widely accepted that MM evolves in all patients from a pre-existing MGUS stage, although in many MM patients this premalignant stage might be unrecognized clinically owing to its asymptomatic nature. We found that MGUS-hMSCs did not show significantly decreased osteoblastogenic differentiation, which suggested that the abnormality of MM-hMSCs is mostly ‘acquired’ during or after the transition from MGUS to MM. Our data do not allow to conclude whether the impaired osteogenic differentiation of MM-hMSCs is due to an inherent difference, although the genomic profile in ND-hMSCs and MM-hMSCs was reported to be much different.4 We assume that with the persistent stimulation of MM cells in vivo, hMSCs gradually gain abnormalities in gene expression and/or certain signaling pathways of osteoblast differentiation, such as Notch signaling. These abnormalities of MM-hMSCs might still exist in vitro even though MM cells are removed.

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Acknowledgements

We would like to thank Nicole Arras, Angelo Willems, Veerle De Greef, Carin Seynaeve and Orla Gallagher for their expert technical assistance and Professor Zhou Qinghua for his administrative support. Our research work is supported by grants from the FWO-Vlaanderen, Vlaamse Liga tegen Kanker (Stichting Emmanuel Van der Shueren), the Vrije Universiteit Brussel (HOA) and the Scientific Foundation Willy Gepts (WFWG) UZ Brussel. Xu S is supported by CSC-VUB scholarship.

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Authors and Affiliations

  1. Department of Lung Cancer Surgery, Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, PRC

    S Xu

  2. Stem Cell Laboratory-Division Clinical Hematology, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium

    S Xu, K De Veirman, A De Becker & I Van Riet

  3. Department of Hematology and Immunology, Vrije Universiteit Brussel (VUB), Myeloma Center Brussels, Brussels, Belgium

    S Xu, K De Veirman, J Hu, D Xu, E Menu, I Vande Broek, B V Camp, K Vanderkerken & I Van Riet

  4. Department of Human Metabolism, University of Sheffield Medical School, Sheffield, UK

    H Evans, C Buckle & P Croucher

  5. Service d'Hématologie, Centre Hospitalier Universitaire (CHU), Lille, France

    X Leleu

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  1. S Xu
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  2. H Evans
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Correspondence to I Van Riet.

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Xu, S., Evans, H., Buckle, C. et al. Impaired osteogenic differentiation of mesenchymal stem cells derived from multiple myeloma patients is associated with a blockade in the deactivation of the Notch signaling pathway. Leukemia 26, 2546–2549 (2012). https://doi.org/10.1038/leu.2012.126

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