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Telomerase activity in normal leukocytes and in hematologic malignancies
Abstract
Telomeres are essential for function and stability of eukaryotic chromosomes. In the absence of telomerase, the enzyme that synthesizes telomeric DNA, telomeres shorten with cell division, a process thought to contribute to cell senescence and the proliferative crisis of transformed cells. We reported telomere stabilization concomitant with detection of telomerase activity in cells immortalized in vitro and in ovarian carcinoma cells, and suggested that telomerase is essential for unlimited cell proliferation. We have now examined the temporal pattern of telomerase expression in selected hematologic malignancies. We found that, unlike other somatic tissues, peripheral, cord blood, and bone marrow leukocytes from normal donors expressed low levels of telomerase activity. In leukocytes from chronic lymphocytic leukemia (CLL) patients, activity was lower than in controls in early disease, and comparable with controls in late disease. Relative to bone marrow, telomerase activity was enhanced in myelodysplastic syndrome (MDS) and more significantly so in acute myeloid leukemia (AML). Regardless of telomerase levels, telomeres shortened with progression of the diseases. Our results suggest that early CLL and MDS cells lack an efficient mechanism of telomere maintenance and that telomerase is activated late in the progression of these cancers, presumably when critical telomere loss generates selective pressure for cell immortality.
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“Telomerase is primarily active in proliferating cells, hematopoietic stem cells, and rapidly renewing cells [114,115,116].”
From Cell Immortality: In Vitro Effective Techniques to Achieve and Investigate Its Applications and Challenges (2024) · cites this paper as [114]
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Cites
Specific Association of Human Telomerase Activity with Immortal Cells and Cancer
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Self-citationTelomerase activity in human ovarian carcinoma.
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Self-citation
Research works printed but not linked: 2
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Cited by
A survey of telomerase activity in human cancer
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Human telomerase contains evolutionarily conserved catalytic and structural subunits
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Self-citationTelomerase Activity in Hematopoietic Cells Is Associated with Self-Renewal Potential
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Telomerase Activity Concentrates in the Mitotically Active Segments of Human Hair Follicles
Ramirez, R. D., Wright, W. E., Shay, J. W., & Taylor, R. S. (1997) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12285654 · Cited by 174
Recovery of function in osteoarthritic chondrocytes induced by p16INK4a-specific siRNA in vitro
Zhou, H. W. (2004) · Rheumatology · doi:10.1093/rheumatology/keh127 · Cited by 108
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Self-citationTelomerase is active in normal gastrointestinal mucosa and not up-regulated in precancerous lesions
Bachor, C., Bachor, O. A., & Boukamp, P. (1999) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s004320050302 · Cited by 68
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BRD4 inhibitors block telomere elongation
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Metadata
- Authors
- Counter, C., Gupta, J., Harley, C., Leber, B., & Bacchetti, S.
- Affiliations
- Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 1995-05-01
- Volume
- 85
- Issue
- 9
- Pages
- 2315-2320
- ISSN
- 0006-4971
- 1528-0020
- Cited by
- 477
- References
- 7
- Language
- en
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