Telomeres and telomerase in hematologic neoplasia

Oncogene. 2002 Jan 21;21(4):680-7. doi: 10.1038/sj.onc.1205075.

Abstract

Normal hematopoietic cells express telomerase activity, however the presence of telomerase does not necessarily imply stable and thus unchanging telomere length. Gradual telomere loss with aging and rapid cycling of hematopoietic stem cells might contribute to immunosenescence, exhausted hematopoiesis, and increased likelihood of malignant transformation. In leukemias and lymphomas, telomere length may reflect the cellular proliferative history, prior to immortalization. The level of telomerase activity is generally influenced by the fraction of cells in the proliferative pool. Shortened telomeres and high telomerase activity almost always correlates with disease severity in hematologic neoplasias such as relapsed leukemia and high-grade lymphomas, indicating that measurement of telomere length and telomerase activity might be useful to monitor disease condition. Since the mode of action of telomerase inhibitors may require telomeric shortening before induction of apoptosis, anti-telomerase therapy might be helpful for adjuvant therapy following conventional chemotherapy, in vitro purging of neoplastic cells in stem cell transplantation, and treating minimal residual disease. Some promising areas of tissue engineering include rejuvenation of hematopoietic stem cells for improving stem cell transplants or enhancing general immunity for older patients.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Enzyme Inhibitors / therapeutic use
  • Hematologic Neoplasms / enzymology*
  • Hematologic Neoplasms / genetics*
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / physiology
  • Humans
  • Leukemia / enzymology
  • Leukemia / genetics
  • Lymphoma / enzymology
  • Lymphoma / genetics
  • Lymphoproliferative Disorders / enzymology
  • Lymphoproliferative Disorders / genetics
  • Models, Genetic
  • Myelodysplastic Syndromes / enzymology
  • Myelodysplastic Syndromes / genetics
  • Telomerase / antagonists & inhibitors
  • Telomerase / metabolism*
  • Telomere / metabolism*
  • Telomere / ultrastructure

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Telomerase