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


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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  1. Blasco MA (2005) Telomeres and human disease: ageing, cancer and beyond. Nat Rev Genet 6(8):611–622

    Article  CAS  PubMed  Google Scholar 

  2. Brummendorf TH, Balabanov S (2006) Telomere length dynamics in normal hematopoiesis and in disease states characterized by increased stem cell turnover. Leukemia 20(10):1706–1716

    Article  CAS  PubMed  Google Scholar 

  3. Werner B, Beier F, Hummel S, Balabanov S, Lassay L, Orlikowsky T, Dingli D, Brummendorf TH, Traulsen A (2015) Reconstructing the dynamics of hematopoietic stem cells from telomere length distributions. elife 4:e08687

    Article  PubMed  PubMed Central  Google Scholar 

  4. Lowenberg B, Downing JR, Burnett A (1999) Acute myeloid leukemia. N Engl J Med 341(14):1051–1062

    Article  CAS  PubMed  Google Scholar 

  5. Patel JP, Gonen M, Figueroa ME, Fernandez H, Sun Z, Racevskis J, Van Vlierberghe P, Dolgalev I, Thomas S, Aminova O et al (2012) Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med 366(12):1079–1089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG, Lindsley RC, Mermel CH, Burtt N, Chavez A et al (2014) Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med 371(26):2488–2498

    Article  PubMed  PubMed Central  Google Scholar 

  7. Wenn K, Tomala L, Wilop S, Vankann L, Hasenbank C, Frank O, Hochhaus A, Giles FJ, Lange T, Muller MC et al (2015) Telomere length at diagnosis of chronic phase chronic myeloid leukemia (CML-CP) identifies a subgroup with favourable prognostic parameters and molecular response according to the ELN criteria after 12 months of treatment with nilotinib. Leukemia 29:2402–2404

    CAS  PubMed  Google Scholar 

  8. Weidner CI, Lin QL, Koch CM, Eisele L, Beier F, Ziegler P, Bauerschñag DO, Jöckel KH, Erbel TW, Mühleisen TW et al (2014) Aging of blood can be tracked by DNA methylation changes at just three CpG sites. Genome Biol 15(2):R24

    Article  PubMed  PubMed Central  Google Scholar 

  9. Lin Q, Wagner W (2015) Epigenetic aging signatures are coherently modified in cancer. PLoS Genet 11(6):e1005334

  10. Hartmann U, Brummendorf TH, Balabanov S, Thiede C, Illme T, Schaich M (2005) Telomere length and hTERT expression in patients with acute myeloid leukemia correlates with chromosomal abnormalities. Haematologica 90(3):307–316

    CAS  PubMed  Google Scholar 

  11. Brummendorf TH, Ersoz I, Hartmann U, Bartolovic K, Balabanov S, Wahl A, Paschka P, Kreil S, Lahaye T, Berger U et al (2003) Telomere length in peripheral blood granulocytes reflects response to treatment with imatinib in patients with chronic myeloid leukemia. Blood 101(1):375–376

    Article  CAS  PubMed  Google Scholar 

  12. Sakoff JA, De Waal E, Garg MB, Denham J, Scorgie FE, Enno A, Lincz LF, Ackland SP (2002) Telomere length in haemopoietic stem cells can be determined from that of mononuclear blood cells or whole blood. Leuk Lymphoma 43(10):2017–2020

    Article  PubMed  Google Scholar 

  13. Fernandez Garcia MS, Teruya-Feldstein J (2014) The diagnosis and treatment of dyskeratosis congenita: a review. J Blood Med 5:157–167

    PubMed  PubMed Central  Google Scholar 

  14. Alter BP, Giri N, Savage SA, Rosenberg PS (2009) Cancer in dyskeratosis congenita. Blood 113(26):6549–6557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Calado RT, Cooper JN, Padilla-Nash HM, Sloand EM, Wu CO, Scheinberg P, Ried T, Young NS (2012) Short telomeres result in chromosomal instability in hematopoietic cells and precede malignant evolution in human aplastic anemia. Leukemia 26:700–707

    Article  CAS  PubMed  Google Scholar 

  16. Heuser M, Schlarmann C, Dobbernack V, Panagiota V, Wiehlmann L, Walter C, Beier F, Ziegler P, Yun H, Kade S et al (2014) Genetic characterization of acquired aplastic anemia by targeted sequencing. Haematologica 99(9):e165–e167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

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Authors and Affiliations



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.

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Correspondence to Fabian Beier.

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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.

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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).

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  • Telomere biology
  • Telomere
  • Acute myeloid leukemia
  • Hematopoietic stem cells
  • Clonal hematopoiesis