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Telomere length and telomerase complex mutations in pediatric acute myeloid leukemia

Leukemia volume 27, pages 1786–1789 (2013)Cite this article

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Pediatric acute myeloid leukemia (AML) is a heterogeneous malignant disease, characterized by abnormal proliferation and impaired differentiation of myeloid cells. Acquired cytogenetic aberrations such as t(8;21)(q22;q22)/AML-ETO, inv(16)(p13q22)/CBFβ-MYH11, t(15;17)(q22;q21)/PML-RARα, rearrangements involving MLL and molecular aberrations in genes such as FLT3, NPM1, CEBPA and WT1 are involved in AML pathogenesis and are prognostic factors for treatment outcome.

Recently, constitutional loss-of-function mutations in telomerase complex genes have been implicated as risk factors for AML in adults.1 The telomerase complex is expressed in highly proliferative cells, and is responsible for maintaining telomeres, which cap the ends of chromosomes and protect genomic DNA from eroding during cell divisions. Impaired telomerase function can result in extremely short telomeres, limiting the proliferative capacity of progenitor cells, and may lead to chromosomal instability, thus predisposing to malignant transformation.2 This pathogenesis is manifested in dyskeratosis congenita, an inherited bone marrow (BM) failure syndrome in which patients are at increased risk for malignancies, including AML, and in which telomerase complex mutations are etiologic.2

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Acknowledgements

AMA was supported by the KiKa Foundation, Amstelveen, The Netherlands, the René Vogels Foundation, Oirschot, and Erasmus Trustfonds, Rotterdam, The Netherlands. This research was supported in part by the National Institutes of Health (NHLBI) Intramural Research Program.

Author contributions

AMA, RTC, SK, NSY, CMZ, RP, VHJV, MMHE conceived and designed the experiments; AMA, SK performed the experiments; AMA, RTC, CMZ, CW, EC, MZ, RP, VHJV, MMHE analyzed the data; AMA, RTC, NSY, CMZ, CW, SK, EC, AB, KG, GJLK, VH, TWK, DR, JT, MZ, RP, VHJV, MMHE contributed reagents, materials and analysis tools and approved the final version of the paper; AMA, RTC, NSY, VHJV, MMHE wrote the paper.

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Authors and Affiliations

  1. Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands

    A M Aalbers, C M Zwaan, E A Coenen, R Pieters & M M van den Heuvel-Eibrink

  2. Department of Immunology, Erasmus MC, Rotterdam, The Netherlands

    A M Aalbers, K Geleijns & V H J van der Velden

  3. Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA

    A M Aalbers, R T Calado, N S Young, C Wu & S Kajigaya

  4. Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, SP, Brazil

    R T Calado

  5. Department of Hematology, Hôpital Robert Debré, Paris, France

    A Baruchel

  6. Department of Neurology, Erasmus MC, Rotterdam, The Netherlands,

    K Geleijns

  7. Dutch Childhood Oncology Group (DCOG), The Hague, The Netherlands

    V de Haas & G J L Kaspers

  8. Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands

    G J L Kaspers

  9. Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, Amsterdam, The Netherlands

    T W Kuijpers

  10. Department of Pediatric Hematology, Immunology and Infectious Disease, Emma Children’s Hospital, Academic Medical Center, Amsterdam, The Netherlands

    T W Kuijpers

  11. Department of Pediatric Hematology/Oncology, AML-BFM Study Group, Medical School Hannover, Hannover, Germany

    D Reinhardt & M Zimmermann

  12. Department of Pediatric Hematology/Oncology, 2nd Medical School, Charles University, Prague, Czech Republic

    J Trka

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  1. A M Aalbers
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  2. R T Calado
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Corresponding author

Correspondence to M M van den Heuvel-Eibrink.

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Aalbers, A., Calado, R., Young, N. et al. Telomere length and telomerase complex mutations in pediatric acute myeloid leukemia. Leukemia 27, 1786–1789 (2013). https://doi.org/10.1038/leu.2013.57

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