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Myelodysplasias

Both expanded and uncultured mesenchymal stem cells from MDS patients are genomically abnormal, showing a specific genetic profile for the 5q− syndrome

Leukemia volume 23, pages 664–672 (2009)Cite this article

Abstract

The presence of cytogenetic aberrations on mesenchymal stem cells (MSC) from myelodysplastic syndrome (MDS) patients is controversial. The aim of the study is to characterize bone marrow (BM) derived MSC from patients with MDS using: kinetic studies, immunophenotyping, fluorescent in situ hybridization (FISH) and genetic changes by array-based comparative genomic hybridization (array-CGH). In all 36 cases of untreated MDS were studied. MDS–MSC achieved confluence at a significantly slower rate than donor-MSC, and the antigenic expression of CD105 and CD104 was lower. Array-CGH studies showed DNA genomic changes that were proved not to be somatic. These results were confirmed by FISH. To confirm that genomic changes were also present in freshly obtained MSCs they were enriched by sorting BM cells with the following phenotype: CD45−/CD73++/CD34−/CD271++. They also showed genomic changes that were confirmed by FISH. To analyze the relationship of these aberrations with clinical–biological data an unsupervized hierarchical cluster analysis was performed, two clusters were identified: the first one included the 5q− syndrome patients, whereas the other incorporated other MDS. Our results show, for the first time that MSC from MDS display genomic aberrations, assessed by array-CGH and FISH, some of them specially linked to a particular MDS subtype, the 5q− syndrome.

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Acknowledgements

We thank Dr JG Briñon for his assistance with the chondrocytic staining; Dr J Almeida for her assistance with the immunophenotypic studies and Irene Rodriguez and Sara González for their assistance with the array-CGH studies. This work was partially supported by JCyL Grants JA10 (Estudio de las células stem mesenquimales en los síndromes mielodisplásicos, interacción con los progenitors hematopoyéticos 2005–2006) and HUS02A07 (Células stem mesenquimales en los síndromes mielodisplásicos: papel en la patogenia de la enfermedad 2007–2009).

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Authors and Affiliations

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

    O Lopez-Villar, F M Sanchez-Guijo, E M Villaron, P Hernández-Campo, N Lopez-Holgado, M Diez-Campelo, J A Perez-Simon, J M Hernández-Rivas, J F San-Miguel & M-C del Cañizo

  2. Centro de Investigación del Cancer CIC/CSIC, University of Salamanca, Salamanca, Spain

    J L Garcia, C Robledo, M V Barbado, J M Hernández-Rivas & J F San-Miguel

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

    O Lopez-Villar, F M Sanchez-Guijo, E M Villaron, P Hernández-Campo, N Lopez-Holgado, M V Barbado, J A Perez-Simon & M-C del Cañizo

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  1. O Lopez-Villar
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Correspondence to M-C del Cañizo.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Lopez-Villar, O., Garcia, J., Sanchez-Guijo, F. et al. Both expanded and uncultured mesenchymal stem cells from MDS patients are genomically abnormal, showing a specific genetic profile for the 5q− syndrome. Leukemia 23, 664–672 (2009). https://doi.org/10.1038/leu.2008.361

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