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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 volume 29, pages 2402–2404 (2015)Cite this article

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The telomere complex consists of repetitive DNA sequences and associated proteins and is located at the end of eukaryotic chromosomes. Telomeres shorten with every cell division and thereby both reflect and restrict the proliferative capacity of somatic cells. Critically short telomeres are associated with genetic instability and eventually, replicative senescence. In chronic myeloid leukemia (CML), increased cellular turnover of clonal breakpoint cluster region-Abelson Murine Leukemia Viral Oncogene Homolog 1 (BCR-ABL)-positive hematopoietic stem and progenitor cells leads to significantly shortened telomeres in peripheral blood myeloid cells.1 Accelerated telomere shortening was found to correlate with disease stage, cytogenetic remission status, progression to accelerated phase and blast crisis as well as clinical risk score at diagnosis in retrospective trials (refs 1, 2, 3, reviewed in ref. 4). However, whether telomere length (TL) can be used as prognostic indicator and/or to predict for depth and kinetics of response to tyrosine kinase inhibitor therapy in patients with CML has not been studied prospectively to date.

Consequently, the aim of this substudy within the ENEST1st trial (NCT01061177) was to investigate, whether average TL in peripheral blood leukocytes at diagnosis measured by monochrome multiplex quantitative PCR (MM-qPCR) can be used as an independent prognostic and/or predictive biomarker in patients with CML undergoing first-line treatment with nilotinib.

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Acknowledgements

This study was sponsored by a grant from Novartis as part of the ENEST1st scientific substudy program.

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Author notes

  1. K Wenn, L Tomala, S Wilop, P Ziegler and T H Brümmendorf: These authors contributed equally to this work.

Authors and Affiliations

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

    K Wenn, L Tomala, S Wilop, L Vankann, C Hasenbank, S Koschmieder, F Beier, P Ziegler & T H Brümmendorf

  2. Novartis Pharma GmbH, Nürnberg, Germany

    O Frank

  3. Department of Hematology/Oncology, Universitätsklinikum Jena, Jena, Germany

    A Hochhaus

  4. Northwestern Medicine Developmental Therapeutics Institute, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, USA

    F J Giles

  5. Department of Hematology and Oncology, University of Leipzig, Leipzig, Germany

    T Lange

  6. Department of Hematology/Oncology, Universitätsmedizin, Mannheim, Germany

    M C Müller

  7. Institute for Occupational and Social Medicine, Aachen University, Aachen, Germany

    P Ziegler

Authors
  1. K Wenn
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Corresponding author

Correspondence to T H Brümmendorf.

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Competing interests

SW has an advisory role for Astellas, Merck and Janssen, he receives research funding from Enceladus and travel is sponsored by Merck and Celgene. OF is a Novartis employee. AH receives research funding from Novartis, BMS, Ariad, Pfizer and MSD. FJG is a consultant for Novartis and receives research funding by Novartis. TL receives honoraria from Novartis, BMS, Pfizer and Ariad and research funding from Novartis. MCM receives honoraria and research funding from Ariad, BMS and Novartis. SK is a consultant and member on an entity’s Board of Directors or advisory committees for Novartis and receives honoraria and research funding by Novartis. THB is a consultant and receives honoraria from Ariad, BMS, Novartis and Pfizer, he holds patents and royalties at Novartis and receives research funding from Novartis. The remaining authors declare no conflict of interest.

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Wenn, K., Tomala, L., Wilop, S. et al. 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 (2015). https://doi.org/10.1038/leu.2015.245

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