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Activation of telomerase in human lymphocytes and hematopoietic progenitor cells
Abstract
This is the first report describing up-regulation of telomerase activity in human normal cells. Telomerase, a ribonucleoprotein enzyme, has been thought to be involved in maintaining telomere length stability in germline and most cancer cells, but not in normal cells. However, in the present study, we demonstrate that telomerase activity is detectable at low levels in normal human T and B cells, increases by in vitro mitogenic stimulation, increases in hematopoietic progenitor cells upon their proliferation and differentiation, and decreases with aging. Understanding the regulation of telomerase activity in normal cells may provide important insights not only into the mechanisms of normal cellular senescence but also into the mechanisms of telomerase activity deregulation as part of cancer development.
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“Although we have to wait for the final report of the clinical trial, no significant adverse effects on normal tissues have been reported so far, even in hematopoietic cells, which may be highly susceptible to Telomelysin due to the presence of telomerase-positive stem cells. (35)”
From Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers (2008) · cites this paper as [35]
In the citing paper
“We should consider the fact that some normal cells, including some tissue stem cells, express relatively high levels of telomerase, (35,36,117) raising questions regarding the safety of Telomelysin.”
From Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers (2008) · cites this paper as [35]
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Self-citationTelomerase activity as a marker for malignancy in feline tissues
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ResultCross-species Association Between Telomere Length and Glucocorticoid Exposure
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BackgroundJang, H. S., Oh, C. K., Jo, J. H., et al. (2001) · Journal of Korean Medical Science · doi:10.3346/jkms.2001.16.5.623 · Cited by 20
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BackgroundInduction of telomerase activity during regeneration after partial hepatectomy in the rat
Tsujiuchi, T., Tsutsumi, M., Kido, A., Takahama, M., Sakitani, H., Iki, K., Sasaki, Y., Denda, A., & Konishi, Y. (1998) · Cancer Letters · doi:10.1016/s0304-3835(97)00378-9 · Cited by 20
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“After in vitro stimulation of normal peripheral mononuclear blood cells, above all T and B lymphocytes, a telomerase activation can be demonstrated which varies with the age of the test person [35] and depends on the nature of the stimulation [5,32,35,48,86,97].”
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BackgroundTelomerase activation and cancer
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“All statistical analyses were performed with the Statistical Package for Social Sciences (SPSS, version 11.0, Chicago, IL, USA).”
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Self-citationDecrease of Telomere Length in Thyroid Adenomas without Telomerase Activity
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“Telomerase activity has been reported in germline cells and embryonic tissues (9), in somatic cells with a high proliferation capacity ( 10 , 11), in immortal cell lines (12), and in a large number of human malignant tumors (13‐15).”
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“…activity in normal somatic tissues have been found in bone marrow and peripheral blood leukocytes [Broccoli et al., 1995; Counter et al., 1995; Hiyama et al., 1995], epidermis [Harle-Bachor and Boukamp, 1996] as well as in cells that have ‘‘replenishing’’ roles such as cells in the skin and…”
BackgroundDiagnostic implications of telomerase activity in pleural effusions
Dıkmen, G., Di̇kmen, E., Kara, M., et al. (2003) · European Respiratory Journal · doi:10.1183/09031936.03.00001303 · Cited by 18
“The intense infiltration of lymphocytes and leukocytes in tuberculosis effusions and empyemas, respectively, might explain the false-positive telomerase activity in these samples [ 22 ].”
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“Pictures were taken at 100X magnification with multiple Z-stack (5-10) at 0.4 µm intervals using an Axiovert 200M Fluorescent Microscope (Carl Zeiss).”
MethodInfluentialSelf-citationA novel molecular therapy using bioengineered adenovirus for human gastrointestinal cancer.
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“These results suggest that normal lymphocytes in the regional lymph nodes could be strictly protected from Telomelysin-induced oncolysis because lymphocytes are not subject to Telomelysin infection and viral replication is also unlikely to occur in normal cells due to their low telomerase activity [20].”
Telomeres and telomerase in normal and malignant B‐cells
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“In these specific cell subtypes, the telomeric checkpoint should be at least temporarily released, to avoid a dramatic loss of functional performances [84,85] (Table 1).”
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Telomerase RNA expression during progression of gastric cancer
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“At the same time, continuous proliferation of stem cells is ensured by a high telomerase activity (Hiyama et al., 1995; Bonatz et al., 1998).”
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Usefulness of Immunological Detection of the Human Telomerase Reverse Transcriptase
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“TRAP assay, however, suffers from some drawbacks, the most important being the rate of false positive results when the analysis includes contaminating telomerase-positive nontumour cells [7,9,31].”
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“Addition of IL-2 to PHAactivated T cells has been reported to facilitate telomerase activity ( 27 , 29, 31).”
BackgroundAviv, A., & Harley, C. B. (2001) · Current Hypertension Reports · doi:10.1007/s11906-001-0029-3 · Cited by 16
Screening for Oral Cancer Using Electrochemical Telomerase Assay
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“By contrast, telomerase activity in the normal mouse differs from that in the adult human [Broccoli et al., 1995; Hiyama et al., 1995; Wright et al., 1996; Roger et al., 1998]: in the normal mouse, telomerase activity exists in the colon, liver, ovary, and testis but not in the brain, heart,…”
BackgroundOn the Genesis of Neuroblastoma and Glioma
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“These data conflict with the findings of some other research groups who were able to detect telomerase activity in PBMC freshly isolated from RA patients and HC [16,22,25].”
ResultLee, B., Wang, S., Choi, J.-S., et al. (2006) · American Journal of Clinical Oncology · doi:10.1097/01.coc.0000207372.64733.b0 · Cited by 15
“Although the telomerase activity has been detected in normal human PBMCs, increased telomerase expression has been observed in PBMCs of laryngeal cancer patients.(9,10) In this study, the rate of telomerase expression was significantly higher in the PBMCs of head and neck cancer patients than the healthy volunteer gro…”
BackgroundDetection of hTERT protein by flow cytometry
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Telomerase activity in human hematopoietic progenitor cells.
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“However, telomerase activity increases upon lymphocyte activation and during the stem cell proliferation and differentiation process.(31) PB granulocytes and monocytes do not express telomerase activity.”
BackgroundSieburg, H. B., Cattarossi, G., & Müller‐Sieburg, C. E. (2013) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003006 · Cited by 13
“Yet, HSCs and other stem cells, express telomerase [11–14].”
BackgroundBone Marrow Stromal Cell (BMSC) and skeletal aging: Role of telomerase enzyme
Saeed, H. (2014) · Pakistan Journal of Pharmaceutical Sciences · doi:10.36721/pjps/27/2/2014/2236/321-333 · Cited by 13
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T‐cell telomere length maintained in HIV‐infected long‐term survivors
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“Peripheral lymphocytes have been reported to have telomerase activity [7].”
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Adhesion of aspirated tumor cells to extracellular matrix proteins
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“Telomerase is also expressed in germ cells and various stem and progenitor cells, but is downregulated during differentiation (Hiyama et al., 1995; Wright et al., 1996).”
BackgroundTelomerase as a tumor-associated antigen for cancer immunotherapy
Patel, K. P., & Vonderheide, R. H. (2004) · Cytotechnology · doi:10.1007/s10616-004-5132-2 · Cited by 12
“topoietic progenitor cells (Broccoli et al. 1995; Hiyama et al. 1995 ), keratinocytes (Harle-Bachor and Boukamp 1996; Yasumoto et al. 1996), and activated B-lymphocytes (Vonderheide et al. 1999).”
BackgroundFabricius (2009) · International Journal of Oncology · doi:10.3892/ijo_00000254 · Cited by 13
“had demonstrated a limited correlation between telomerase activity and lymphocyte infiltration in tumor margin tissues (13,14,94,95).”
BackgroundInfluentialInteraction between Bovine leukemia virus (BLV) infection and age on telomerase misregulation
Hemmatzadeh, F., Keyvanfar, H., Hasan, N. H., Niap, F., Hassan, E. B., Hematzade, A., Ebrahimie, E., McWhorter, A. R., & Ignjatovic, J. (2015) · Veterinary Research Communications · doi:10.1007/s11259-015-9629-2 · Cited by 13
Telomerase inhibitors in anticancer therapy: Gossypol as a potential telomerase inhibitor
Mego, M. (2002) · Bratislavské lekárske listy/Bratislava medical journal · doi:10.1007/bf03656559 · Cited by 13
Telomerase activity in peripheral blood mononuclear cells from patients with SLE
Kurosaka, D., OZAWA, Y., YASUDA, J., YOKOYAMA, T., YAMADA, A., AKIYAMA, M., SAITO, S., & TAJIMA, N. (2001) · Annals of the Rheumatic Diseases · doi:10.1136/ard.60.12.1158 · Cited by 12
Self-citationIkeguchi, M., Unate, H., Maeta, M., & Kaibara, N. (1999) · Langenbeck s Archives of Surgery · doi:10.1007/s004230050242 · Cited by 12
“Non-neoplastic peripheral lymphocytes have been reported to have telomerase activity [24].”
BackgroundTelomere dynamics and cytogenetic changes in human hematologic neoplasias: A working hypothesis
Ohyashiki, K., & Ohyashiki, J. H. (1997) · Cancer Genetics and Cytogenetics · doi:10.1016/s0165-4608(96)00277-4 · Cited by 14
Zhang, K., Hou, R., Niu, X., et al. (2010) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2010.09790.x · Cited by 12
Metadata
- Authors
- Hiyama, K., Hirai, Y., Kyoizumi, S., Akiyama, M., Hiyama, E., Piatyszek, M. A., Shay, J. W., Ishioka, S., & Yamakido, M.
- Affiliations
- Hiroshima University (JP)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1995-10
- Volume
- 155
- Issue
- 8
- Pages
- 3711-3715
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1516272650
- Cited by
- 853
- References
- 0
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 10 · 2022: 6 · 2021: 11 · 2020: 9 · 2019: 13 · 2018: 11 · 2017: 8 · 2016: 13 · 2015: 15 · 2014: 17 · 2013: 20 · 2012: 17
- FWCI
- 38.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG07992, R01AG007992)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- telomerase, telomerase activity, lymphocytes, T cells, B cells, hematopoietic progenitor cells, mitogen stimulation, aging, cellular senescence, telomere length, carcinogenesis, normal cells
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Base Sequence, Bone Marrow Cells, Cell Separation, Child, Child, Preschool, Enzyme Activation, Hematopoietic Stem Cells, Humans, Infant, Infant, Newborn, Leukocytes, Mononuclear, Lymphocyte Activation, Lymphocytes, Male, Middle Aged, Molecular Sequence Data, Telomerase
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