Granulocyte colony-stimulating factor administration upregulates telomerase activity in CD34+ haematopoietic cells and may prevent telomere attrition after chemotherapy

Br J Haematol. 2003 Jan;120(2):329-36. doi: 10.1046/j.1365-2141.2003.04043.x.


Hematopoietic reconstitution could be associated with premature ageing of the transplanted cells and a high frequency of myelodysplastic syndrome and secondary leukaemia. Telomere length decreases with cell divisions and age, and at a crucial length it is associated with chromosomal instability and cell senescence. Telomerase is a reverse transcriptase enzyme that adds nucleotides to chromosomal ends. Most somatic cells lack telomerase activity yet haematopoietic stem cells retain low levels of telomerase. Some studies have found that chemotherapy and stem cell transplantation lead to the accelerated shortening of telomere length. As granulocyte colony-stimulating factor (G-CSF) is routinely used in the mobilization of stem cells for transplantation, we evaluated its effects on telomerase activity and regulation, and on telomere dynamics, in normal donors and selected lymphoma patients. Administration of G-CSF increased telomerase activity in CD34+ haematopoietic cells compared with controls. In marrow-derived CD34+ cells, telomerase activity increased sevenfold, compared with a 14-fold increase in peripheral-blood-mobilized CD34+ cells. A parallel increase in the expression of human telomerase enzyme reverse transcriptase RNA and protein kinase C alpha occurred. In addition, G-CSF administration to five lymphoma patients after consecutive courses of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy, resulted in telomere length preservation or elongation, as opposed to marked attrition in patients who did not receive growth factors. We conclude that the in vivo administration of G-CSF prevents or attenuates telomere attrition associated with chemotherapy administration. This attenuation may contribute to the preservation of telomere integrity inG-CSF-primed transplanted stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, CD34*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / enzymology
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Enzyme Activation
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Hematopoietic Stem Cell Mobilization*
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / enzymology*
  • Hematopoietic Stem Cells / immunology
  • Humans
  • Lymphoma / drug therapy
  • Lymphoma / enzymology*
  • Lymphoma / immunology
  • Middle Aged
  • Prednisone / administration & dosage
  • Protein Kinase C / genetics
  • Protein Kinase C-alpha
  • RNA / analysis
  • Telomerase / genetics
  • Telomerase / metabolism*
  • Telomere / genetics
  • Telomere / ultrastructure
  • Vincristine / administration & dosage


  • Antigens, CD34
  • Granulocyte Colony-Stimulating Factor
  • Vincristine
  • RNA
  • Doxorubicin
  • Cyclophosphamide
  • PRKCA protein, human
  • Protein Kinase C
  • Protein Kinase C-alpha
  • Telomerase
  • Prednisone

Supplementary concepts

  • CHOP protocol