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Evidence for a pre-existing telomere deficit in non-clonal hematopoietic stem cells in patients with acute myeloid leukemia

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Abstract

Telomere shortening represents an established mechanism connecting aging and cancer development. We sequentially analyzed telomere length (TL) of 49 acute myeloid leukemia (AML) patients at diagnosis (n = 24), once they achieved complete cytological remission (CCR) and/or during refractory disease or relapse and after 1-year follow-up, with all patients having at least two sequential samples. TL was analyzed by monochrome multiplex quantitative polymerase chain reaction. We have observed substantially shortened TL in the cells of patients at diagnosis compared to age-adjusted controls. In patients reaching CCR after chemotherapy, telomere shortening was less pronounced than in persistence or relapse but still significantly shortened compared to controls. We estimate patients harboring approximately 20 years of premature telomere loss compared to healthy aged-matched subjects at the time of AML onset. Our data indicate a pre-existing telomere deficit in non-clonal hematopoiesis of AML patients providing a link between age and AML development.

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Acknowledgments

We are thankful to the Excellence Initiative of the RWTH Aachen University for the RWTH StartUp funding to Fabian Beier.

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Author notes

  1. MSVF, MC, and PZ contributed equally to this work

Authors and Affiliations

  1. Department of Hematology, Oncology, Haemostaseology and Stem Cell Transplantation, RWTH Aachen University Medical Faculty, Aachen, Germany

    Mónica S. Ventura Ferreira, Martina Crysandt, Patrick Ziegler, Sebastian Hummel, Stefan Wilop, Martin Kirschner, Mirle Schemionek, Edgar Jost, Tim H. Brümmendorf & Fabian Beier

  2. Institute for Occupational and Social Medicine, RWTH Aachen University, Aachen, Germany

    Patrick Ziegler

  3. Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical Faculty, Aachen, Germany

    Wolfgang Wagner

  4. Institute for Biomedical Technology, Cell Biology, RWTH Aachen University Medical Faculty, Aachen, Germany

    Wolfgang Wagner

Authors
  1. Mónica S. Ventura Ferreira
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  2. Martina Crysandt
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  3. Patrick Ziegler
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  4. Sebastian Hummel
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  5. Stefan Wilop
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  6. Martin Kirschner
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  7. Mirle Schemionek
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  8. Edgar Jost
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  9. Wolfgang Wagner
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  10. Tim H. Brümmendorf
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  11. Fabian Beier
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Contributions

MSVF, MC, and PZ performed the experiments, analyzed and interpreted the data and wrote the manuscript; SH, SW, EJ, MK, MS, and WW contributed to quality assurance, clinical data and material collection, writing of the manuscript; THB analyzed and interpreted the data, wrote the manuscript, and provided financial support; FB conceived and planned the study design, interpreted the data, and wrote the manuscript.

Corresponding author

Correspondence to Fabian Beier.

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Disclosures

W. Wagner for Cygenia GmbH: employment, equity ownership, patents, and royalties. The Medical School of the RWTH Aachen University has a pending patent for the EAS.

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Supplementary Table 1

Patient’s characteristics of the 49 de novo acute myeloid leukemia (AML) patients. Data not available (n.a.). (DOCX 16 kb).

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Ventura Ferreira, M.S., Crysandt, M., Ziegler, P. et al. Evidence for a pre-existing telomere deficit in non-clonal hematopoietic stem cells in patients with acute myeloid leukemia. Ann Hematol 96, 1457–1461 (2017). https://doi.org/10.1007/s00277-017-3049-z

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  • DOI: https://doi.org/10.1007/s00277-017-3049-z

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