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Myeloma

CD29 expressed on plasma cells is activated by divalent cations and soluble CD106 contained in the bone marrow plasma: refractory activation is associated with enhanced proliferation and exit of clonal plasma cells to circulation in multiple myeloma patients

Leukemia volume 26, pages 1098–1105 (2012)Cite this article

Abstract

Malignant plasma cells (PC) in human multiple myeloma (MM) are retained in the bone marrow (BM) microenvironment. Using HUTS21 monoclonal antibody that reacts with active CD29 integrin, we demonstrate that this active form is tightly regulated by divalent cations and soluble CD106 (sCD106) contained in the BM plasma. Moreover, we also show that in vivo expression of the active CD29 on PC was clearly diminished in a minority of MM cases (HUTS21− patients). HUTS21− cells were refractory to the addition of either normal allogeneic BM plasma or optimal concentrations of exogenous divalent cations and recombinant sCD106. Furthermore, a lower binding to fibronectin was detected in comparison with HUTS21+ PC. On the other hand, although HUTS21− PC showed a reduced amount of total (active+inactive) CD29, western-blot assays demonstrated that these clonal PC contained the two species of CD29, with molecular masses of 110 and 130 kDa, which were expressed on normal or HUTS21+ PC. Finally, we detected a clear association between the presence of HUTS21− PC in the BM and an increased percentage of circulating PC with a high proliferative index, emphasizing the essential role of CD29 in the pathogenesis and progression of this disease.

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Acknowledgements

We thank Pilar Salillas, Eva Gallo, Francine Doat and Carmen Quellez for their excellent technical assistance. I also thank the scientific friends whose life and teaching inspired me like the blue and clear light of wisdom. Finally, I owe an unpayable debt for all my life to Ernesto Roldán Chala, who taught me so much about patience, perseverance and responsibility. This work was supported by the Spanish Fondo de Investigaciones Sanitarias (FIS) with the Grant G03/136. EMV was supported by a grant from the Hospital Ramón y Cajal Foundation.

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  1. Servicio de Inmunología, Hospital Ramón y Cajal, Madrid, Spain

    E Martínez-Viñambres, J A García-Trujillo, E Rodríguez-Martín, L M Villar, J Coll & E Roldán

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EM-V designed research, performed research, analyzed data; JAG-T designed research, performed research, analyzed data; ER-M analyzed data; LMV designed research, analyzed data; JC analyzed data; ER designed research, analyzed data, wrote the paper.

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Martínez-Viñambres, E., García-Trujillo, J., Rodríguez-Martín, E. et al. CD29 expressed on plasma cells is activated by divalent cations and soluble CD106 contained in the bone marrow plasma: refractory activation is associated with enhanced proliferation and exit of clonal plasma cells to circulation in multiple myeloma patients. Leukemia 26, 1098–1105 (2012). https://doi.org/10.1038/leu.2011.335

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