Dysfunctional telomeres and hematological disorders

Differentiation. Mar-Apr 2018;100:1-11. doi: 10.1016/j.diff.2018.01.001. Epub 2018 Jan 4.


Telomere biology disorders, which are characterized by telomerase activity haploinsufficiency and accelerated telomere shortening, most commonly manifest as degenerative diseases. Tissues with high rates of cell turnover, such as those in the hematopoietic system, are particularly vulnerable to defects in telomere maintenance genes that eventually culminate in bone marrow (BM) failure syndromes, in which the BM cannot produce sufficient new blood cells. Here, we review how telomere defects induce degenerative phenotypes across multiple organs, with particular focus on how they impact the hematopoietic stem and progenitor compartment and affect hematopoietic stem cell (HSC) self-renewal and differentiation. We also discuss how both the increased risk of myelodysplastic syndromes and other hematological malignancies that is associated with telomere disorders and the discovery of cancer-associated somatic mutations in the shelterin components challenge the conventional interpretation that telomere defects are cancer-protective rather than cancer-promoting.

Keywords: DNA damage response; Hematopoietic stem cells; Myelodysplastic syndrome; Telomere biology disorders.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bone Marrow Diseases / genetics*
  • Bone Marrow Diseases / pathology
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Telomere / genetics
  • Telomere / metabolism
  • Telomere / pathology
  • Telomere Shortening*