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Ann Hematol. 2017 Sep;96(9):1457-1461. doi: 10.1007/s00277-017-3049-z. Epub 2017 Jul 3.

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

Author information

1
Department of Hematology, Oncology, Haemostaseology and Stem Cell Transplantation, RWTH Aachen University Medical Faculty, Aachen, Germany.
2
Institute for Occupational and Social Medicine, RWTH Aachen University, Aachen, Germany.
3
Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical Faculty, Aachen, Germany.
4
Institute for Biomedical Technology, Cell Biology, RWTH Aachen University Medical Faculty, Aachen, Germany.
5
Department of Hematology, Oncology, Haemostaseology and Stem Cell Transplantation, RWTH Aachen University Medical Faculty, Aachen, Germany. fbeier@ukaachen.de.

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.

KEYWORDS:

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

PMID:
28674830
DOI:
10.1007/s00277-017-3049-z
[Indexed for MEDLINE]

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