Journal of Molecular Medicine

, Volume 88, Issue 3, pp 249–265 | Cite as

Leukemia-associated genetic aberrations in mesenchymal stem cells of children with acute lymphoblastic leukemia

  • Shabnam Shalapour
  • Cornelia Eckert
  • Karl Seeger
  • Madlen Pfau
  • Javier Prada
  • Günter Henze
  • Thomas Blankenstein
  • Thomas Kammertoens
Original Article

Abstract

Childhood acute lymphoblastic leukemia (ALL) is caused by malignant immature lymphocytes. Even though childhood ALL can be cured in a large number of patients, around 20% of the patients suffer a relapse after chemotherapy. The origin of the relapse is unclear at the present time. Given the high plasticity of cells, we searched for leukemia-associated genetic aberrations and immunoglobulin (IG) gene rearrangements in mesenchymal stem cells (MSC) from childhood B-cell precursor ALL patients. MSC from all ten ALL patients analyzed presented the chromosomal translocations that had been detected in leukemia cells (TEL-AML1, E2A-PBX1, or MLL rearrangement). The proportions of translocation-positive MSC varied between 10% and 54% depending on the patients and the time point of analysis. Leukemia-specific IG gene rearrangements were detected in the MSC from three ALL patients. The detection of leukemia-associated genetic aberrations in MSC indicates a clonal relationship between MSC and leukemia cells and suggests their involvement in the pathogenesis and/or pathophysiology of childhood ALL.

Keywords

Mesenchymal stem cells Fusion genes Childhood acute lymphoblastic leukemia Chromosomal translocations IG gene rearrangements 

Notes

Acknowledgments

The authors are grateful to S. Tuerkmen for metaphase analysis and M. Nagy for chimerism analysis and to R. Marschalek for MLL sequence analysis. We thank the staff members of the ALL-REZ BFM study group, Shidokht Shalapour, T. Schüler, and L. Bastian for their support. This work was supported by the DFG Sonderforschungsbereich TR 36 and the Deutsche Krebshilfe (Bonn, Germany).

Authorship

Contribution: S.S. designed, performed, analyzed experiments, and wrote the manuscript; T.B. designed, analyzed experiments, and wrote the manuscript; T.K. analyzed experiments and wrote the manuscript; C.E. and M.P. performed experiments; and C.E. and J.P. analyzed experiments and wrote the manuscript. G.H. coordinates the ALL-relapse-BFM study; K.S. and G.H. collected clinical data used in this study and analyzed data.

Conflict of interest disclosure

The authors declare no competing financial interests.

Supplementary material

109_2009_583_MOESM1_ESM.pdf (4.7 mb)
ESM (PDF 4.72 mb)

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Shabnam Shalapour
    • 1
    • 2
  • Cornelia Eckert
    • 1
  • Karl Seeger
    • 1
  • Madlen Pfau
    • 1
  • Javier Prada
    • 1
  • Günter Henze
    • 1
  • Thomas Blankenstein
    • 2
    • 3
  • Thomas Kammertoens
    • 2
    • 3
  1. 1.Department of Pediatric Oncology and HematologyCharité-Universitätsmedizin BerlinBerlinGermany
  2. 2.Institute of Immunology, Charité-Universitätsmedizin BerlinCampus Benjamin-FranklinBerlinGermany
  3. 3.Max-Delbrück Center for Molecular MedicineBerlinGermany

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