Short telomeres: from dyskeratosis congenita to sporadic aplastic anemia and malignancy

Transl Res. 2013 Dec;162(6):353-63. doi: 10.1016/j.trsl.2013.05.003. Epub 2013 Jun 1.


Telomeres are DNA-protein structures that form a protective cap on chromosome ends. As such, they prevent the natural ends of linear chromosomes from being subjected to DNA repair activities that would result in telomere fusion, degradation, or recombination. Both the DNA and protein components of the telomere are required for this essential function, because insufficient telomeric DNA length, loss of the terminal telomeric DNA structure, or deficiency of key telomere-associated factors may elicit a DNA damage response and result in cellular senescence or apoptosis. In the setting of failed checkpoint mechanisms, such DNA-protein defects can also lead to genomic instability through telomere fusions or recombination. Thus, as shown in both model systems and in humans, defects in telomere biology are implicated in cellular and organismal aging as well as in tumorigenesis. Bone marrow failure and malignancy are 2 life-threatening disease manifestations in the inherited telomere biology disorder dyskeratosis congenita. We provide an overview of basic telomere structure and maintenance. We outline the telomere biology defects observed in dyskeratosis congenita, focusing on recent discoveries in this field. Last, we review the evidence of how telomere biology may impact sporadic aplastic anemia and the risk for various cancers.

Keywords: AML; CLL; CST; CTC1; CTC1/STN1/TEN1; DC; FA; FISH; Fanconi anemia; MDS; O/E; POT1; Q-PCR; RAP1; RTEL1; STN1; TEN1; TERC; TERF1 (TRF1)-interacting nuclear factor 2; TERT; TIN2; TIN2-interacting protein 1; TINF2; TPP1; TRF1; TRF1-interacting protein 2; TRF2; acute myeloid leukemia; base pairs; bp; chronic lymphocytic leukemia; conserved telomere maintenance component 1; dyskeratosis congenita; fluorescence in situ hybridization; myelodysplastic syndrome; odds over expected ratio; protection of telomeres 1; quantitative polymerase chain reaction; regulator of telomere elongation helicase 1; repressor/activator protein 1; suppressor of cdc13-1; telomerase RNA component; telomerase reverse transcriptase; telomeric pathway with STN1; telomeric repeat factor 1; telomeric repeat factor 2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / genetics
  • Aging / physiology
  • Anemia, Aplastic / etiology*
  • Dyskeratosis Congenita / etiology*
  • Humans
  • Mutation
  • Neoplasms / etiology*
  • Risk Factors
  • Shelterin Complex
  • Telomerase / genetics
  • Telomerase / physiology
  • Telomere Shortening* / genetics
  • Telomere Shortening* / physiology
  • Telomere-Binding Proteins
  • Translational Research, Biomedical


  • ACD protein, human
  • Shelterin Complex
  • Telomere-Binding Proteins
  • Telomerase