The effect of chemotherapy on telomere dynamics: clinical results and possible mechanisms

Leuk Lymphoma. 2013 Sep;54(9):2023-9. doi: 10.3109/10428194.2012.757765. Epub 2013 Jan 7.

Abstract

Telomeres are the chromosomal end components, and their length in hematopoietic stem cells correlates with the bone marrow proliferative reserve. There are few data regarding telomere dynamics in hematopoietic stem cells after exposure to chemotherapy. We show that the attrition of telomeres after cytotoxic treatment correlates with the intensity of chemotherapy. Using cytotoxic drugs with differential effects on hematopoietic stem cells, our data imply that chemotherapy-induced telomere shortening results from direct damage to hematopoietic stem cells and/or the induction of proliferative stress on bone marrow while sparing repopulating stem cells. These results gain importance considering the current long survival of patients with cancer.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Case-Control Studies
  • Female
  • Fluorouracil / administration & dosage
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyotype
  • Male
  • Middle Aged
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Telomere / drug effects*
  • Telomere / genetics
  • Telomere / metabolism
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives

Substances

  • Antineoplastic Agents
  • Vidarabine
  • fludarabine
  • Fluorouracil