Cancer and myeloid clonal evolution in the short telomere syndromes

Curr Opin Genet Dev. 2020 Feb:60:112-118. doi: 10.1016/j.gde.2020.02.019. Epub 2020 Apr 7.


The short telomere syndromes are considered the most common premature aging disorders. Although studies in genetically modified cells and animal models have suggested telomere dysfunction may promote genome instability, only a minority of humans with inherited loss-of-function mutations in telomerase and related genes develop cancer. Solid tumors are overall rare, and the vast majority of cancers are bone marrow-derived with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) comprising three-quarter of cases. In contrast to young short telomere syndrome patients who develop aplastic anemia, MDS and AML are usually diagnosed in adults who have milder short telomere defects. Here, we dissect the mechanisms by which these two bone marrow failure states, aplastic anemia and MDS-AML, evolve in the setting of varying degrees of telomere shortening. We discuss the implications of these observations for patient care as well as for understanding the genetics and biology of age-related myeloid clonal evolution.

Publication types

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

MeSH terms

  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology*
  • Clonal Evolution*
  • Genomic Instability*
  • Humans
  • Leukemia, Myeloid, Acute / enzymology
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / pathology*
  • Mutation
  • Myelodysplastic Syndromes / enzymology
  • Myelodysplastic Syndromes / genetics
  • Myelodysplastic Syndromes / pathology*
  • Telomerase / genetics
  • Telomerase / metabolism*
  • Telomere*


  • TERT protein, human
  • Telomerase