Abstract
Telomerase activity and telomere length in mononuclear cells (MNCs) and granulocytes from peripheral blood (PB) and bone marrow (BM) specimens were studied in pediatric acute leukemia (ALL, n = 15; AML, n = 1) and pediatric solid tumor (ST) patients (n = 9) at diagnosis, during and after chemotherapy. In four ST patients, tumor tissue was also available. For comparative analysis, MNCs from healthy donors (n = 53) were analyzed. Telomerase was evaluated using a modified telomeric repeat amplification protocol (TRAP) assay, and telomere length by terminal restriction fragment (TRF) analysis. At diagnosis, high telomerase activity was detected in MNCs from all leukemia patients, which was similar to the activity from ST biopsy specimens. This exceeded by 10- to 20-fold the activity in PB MNCs from ST patients and healthy donors (P < 0.05). granulocyte fractions lacked telomerase activity in all groups. bm mncs in leukemia patients revealed a four-fold higher telomerase activity than pb (P = 0.005). After induction chemotherapy and response to treatment, telomerase activity decreased to borderline or undetectable levels in PB MNCs in leukemia (P < 0.01). average telomeres in pb mncs from pediatric patients were significantly longer (n = 25; 10.9 kbp) than telomeres in PB and BM MNCs from adult healthy donors (7.45 kbp) (P < 0.0001). at diagnosis, telomeres were shorter from bm compared to pb specimens in leukemia (P < 0.05), and two peak trfs were observed corresponding to the malignant and normal cell clones. with the attainment of remission, the lower trf peak, reflecting the leukemic population, was lost. in leukemia patients, mean trfs increased on average 2.2 kbp after induction chemotherapy, but decreased thereafter on consolidation and maintenance chemotherapy (1 kbp). this was comparable to an average telomere loss of 1.2 kbp in pb specimens from st patients after chemotherapy. in all patients, telomere loss in granulocytes as compared to mncs was more pronounced with 1.8 vs 1 kbp, respectively (P = 0.014). Our results demonstrate that at diagnosis, telomerase was consistently and highly upregulated in BM and PB specimens in leukemia, decreased after induction therapy, and correlated with remission. BM specimens in leukemia had higher telomerase activity, probably due to the greater leukemic burden than in PB. Telomeres were significantly longer in children than in adults, but shortened as a consequence of chemotherapy with repeated cycles of hematopoietic regeneration. In acute leukemia, with the loss of the leukemic burden after induction chemotherapy, longer mean TRFs were found, a reflection of the repopulation with normal cells. Our findings suggest that telomerase activity may be useful in the management of childhood malignancies. The significance of telomere length shortening in pediatric patients undergoing chemotherapy and possible telomere regeneration after myelosuppressive treatment remain to be determined.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Engelhardt, M., Ozkaynak, M., Drullinsky, P. et al. Telomerase activity and telomere length in pediatric patients with malignancies undergoing chemotherapy. Leukemia 12, 13–24 (1998). https://doi.org/10.1038/sj.leu.2400889
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.leu.2400889
Keywords
This article is cited by
-
Telomere-based treatment strategy of cardiovascular diseases: imagination comes to reality
Genome Instability & Disease (2024)
-
Impact of chemotherapy on telomere length in sporadic and familial breast cancer patients
Breast Cancer Research and Treatment (2015)
-
Telomerase and cancer therapeutics
Nature Reviews Cancer (2008)
-
Telomere length of cord blood-derived CD34+ progenitors predicts erythroid proliferative potential
Leukemia (2007)
-
Telomeres and telomerase in paediatric patients with T-cell acute lymphoblastic leukaemia (T-ALL)
Leukemia (2005)