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Myeloma

Mesenchymal stem cells from multiple myeloma patients display distinct genomic profile as compared with those from normal donors

Leukemia volume 23, pages 1515–1527 (2009)Cite this article

Abstract

It is an open question whether in multiple myeloma (MM) bone marrow stromal cells contain genomic alterations, which may contribute to the pathogenesis of the disease. We conducted an array-based comparative genomic hybridization (array-CGH) analysis to compare the extent of unbalanced genomic alterations in mesenchymal stem cells from 21 myeloma patients (MM-MSCs) and 12 normal donors (ND-MSCs) after in vitro culture expansion. Whereas ND-MSCs were devoid of genomic imbalances, several non-recurrent chromosomal gains and losses (>1 Mb size) were detected in MM-MSCs. Using real-time reverse transcription PCR, we found correlative deregulated expression for five genes encoded in regions for which genomic imbalances were detected using array-CGH. In addition, only MM-MSCs showed a specific pattern of ‘hot-spot’ regions with discrete (<1 Mb) genomic alterations, some of which were confirmed using fluorescence in situ hybridization (FISH). Within MM-MSC samples, unsupervised cluster analysis did not correlate with particular clinicobiological features of MM patients. We also explored whether cytogenetic abnormalities present in myelomatous plasma cells (PCs) were shared by matching MSCs from the same patients using FISH. All MM-MSCs were cytogenetically normal for the tested genomic alterations. Therefore we cannot support a common progenitor for myeloma PCs and MSCs.

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Acknowledgements

We are thankful to Ms Montserrat Martín, Sara González, Irene Rodríguez, Isabel Isidro, Pilar Hernández, Almudena Martín, Montserrat Hernández, Sandra Muntión and Irene Real for their excellent technical work and assistance. We also thank the Genomic Unit (Centro de Investigación del Cáncer, Universidad de Salamanca-CSIC) for spotting, hybridization and scanning of CGH arrays. This work was partially supported by grants from ‘Proyecto Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León (Consejería de Sanidad JCyL–ISCIII)’, the Spanish Myeloma Network Program (RD06/0020/0006), and ‘Grupos de Excelencia de Castilla y León’ (Ref. GR33). MG was supported by the ‘Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+I)’ and the ISCIII-FIS (CP 05/0279). AG-G was supported by the ‘Proyecto Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León (Consejería de Sanidad JCyL–ISCIII)’.

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  1. M Garayoa and J L Garcia: These two authors contributed equally to this work.

Authors and Affiliations

  1. Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, Universidad de Salamanca-CSIC, Salamanca, Spain

    M Garayoa, J L Garcia, A Garcia-Gomez, A Pandiella & J F San Miguel

  2. Unidad de Investigación, Instituto de Estudio de Ciencias de la Salud de Castilla y León (IECSCYL) – Hospital Universitario de Salamanca, Salamanca, Spain

    J L Garcia

  3. Servicio de Hematología. Hospital Universitario de Salamanca., Salamanca, Spain

    C Santamaria, J M Hernández, F M Sanchez-Guijo, M-C del Cañizo, N C Gutiérrez & J F San Miguel

  4. Servicio de Traumatología. Hospital Universitario de Salamanca., Salamanca, Spain

    J F Blanco

  5. Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Salamanca, Spain

    M Garayoa, F M Sanchez-Guijo, M-C del Cañizo & J F San Miguel

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  1. M Garayoa
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Correspondence to M Garayoa.

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Garayoa, M., Garcia, J., Santamaria, C. et al. Mesenchymal stem cells from multiple myeloma patients display distinct genomic profile as compared with those from normal donors. Leukemia 23, 1515–1527 (2009). https://doi.org/10.1038/leu.2009.65

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