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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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Items 301–400 of 859
Telomeres, Telomerase and Chromosome Stability
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BackgroundSelf-citationCell cycle dependent telomere regulation by telomerase in human bone marrow mesenchymal stem cells
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BackgroundTelomerase activity as a measure for monitoring radiocurability of tumor cells
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“Several studies have reported that primitive non-dividing stem cells may not exhibit telomerase activity (Hiyama et al., 1995; Chiu et al., 1996).”
BackgroundTelomerase Activity in Human Thyroid Carcinomas Originating from the Follicular Cells1
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Telomerase activity and telomere length in thyroid neoplasia: biological and clinical implications
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“A persisting source of uncertainty in the above studies is the influence of infiltrating activated lymphocytes, which are known to exhibit telomerase activity [15].”
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Nan-PIng, W., & Hodes, R. J. (2000) · Journal of Clinical Immunology · doi:10.1023/a:1017223602293 · Cited by 49
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“patients with NSCLC identified telomerase activity in 78.6% compared with 4% of adjacent normal tissues ( 21 ).”
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“In fact, T and B lymphocytes are unique among differentiated somatic cell types in terms of their ability to respond to specific or nonspecific stimuli by proliferation and continued expansion, accompanied by TERT upregulation (78, 79).”
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“, 1998), but not in normal somatic cells except in some self-renewing cells with high regenerative potential such as hematopoietic (Hiyama et al., 1995) and endometrial cells (Kyo et al.”
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Self-citationTelomere Dysfunction, Chromosomal Instability and Cancer
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“In adults, telomerase is active in highly proliferative cells, such as the proliferating T lymphocytes [18] and the bulb-containing fragment of hair follicles [14].”
BackgroundSelective Isolation of Young Cells from Human Corneal Endothelium by the Sphere-Forming Assay
Mimura, T., Yamagami, S., Yokoo, S., Usui, T., & Amano, S. (2009) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2009.0608 · Cited by 47
“The level of telomerase activity is associated with the proliferative capacity of cells(38) and in vitro mitogenic stimulation upregulates telomerase activity in human lymphocytes despite the very low telomerase activity of unstimulated lymphocytes.(39) In our present study, little or no telomerase activity was detect…”
Telomerase and mammalian ageing: a critical appraisal
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Telomerase activity in esophageal carcinoma
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Evaluating biomarkers to model cancer risk post cosmic ray exposure
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Urine Telomerase: An Important Marker in the Diagnosis of Bladder Cancer
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“Telomerase activity is present in most human malignant tumors, whereas it is generally not detectable in normal somatic cells [9,10], with the exception of inflammatory elements, germline and hematopoietic stem cells [11,12], cells of the epidermal basal layer [13], and intestinal crypt cells [14,15].”
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“Telomerase activity is maintained in several tissues, such as proliferative cells of renewal tissues and organs stimulated to divide ( Hiyama et al. 1995; Harle-Bacher and Boukamp 1996; Belair et al. 1997; Norrback and Roos 1997; Osonai et al. 2002), although the low level of telomerase activity in such tissues is not…”
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“The telomere loss in most somatic cells reflects limiting levels of telomerase, although activated B and T lymphocytes as well as CD341 progenitor cells express telomerase at detectable levels.(18,19) It has been proposed that although the low telomerase level present in somatic cells is not sufficient to maintain con…”
BackgroundTargeting Telomerase and ATRX/DAXX Inducing Tumor Senescence and Apoptosis in the Malignant Glioma
Fan, H., Chen, C., Chi, C.-S., Tsai, J., Chiang, K.-L., Chang, Y., Lin, S., & Harn, H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20010200 · Cited by 48
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BackgroundTelomerase activity and telomere length of peripheral blood mononuclear cells in SLE patients
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Sirolimus accelerates senescence of endothelial progenitor cells through telomerase inactivation
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Molecular pathways regulating the self-renewal of hematopoietic stem cells
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Senescence and immortalization of human cells
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“Some normal somatic cells, despite exhibiting shortening telomeres when passaged in vitro, have a low level of telomerase activity (Broccoli et al. 1995; Counter et al. 1995; Hiyama et al. 1995; Härle-Bachor and Boukamp 1996; Yasumoto et al. 1996; Hsiao et al. 1997).”
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Inhibition of human telomerase by a retrovirus expressing telomeric antisense RNA
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The Maintenance of Telomere Length in CD28+ T Cells During T Lymphocyte Stimulation
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Human lymphocyte telomerase is genetically regulated
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Self-citationTelomere length and telomerase activity in malignant lymphomas at diagnosis and relapse
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Genes Involved in the Control of Cellular Proliferative Potentiala
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“This activity can be increased by 2–3 orders of magnitude by stimulation of primary leukocytes with phytohemagglutinin (Hiyama et al. 1995).”
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“We have not incorporated such factors in our model because it seems unlikely that similar factors play a significant role in human T cells, which are well known to suffer from telomere shortening, and, ultimately, senescence, by cell division (14, 15, 22–27).”
InfluentialDelhommeau, F., Thierry, A., Feneux, D., Lauret, E., Leclercq, E., Courtier, M. H., Sainteny, F., Vainchenker, W., & Griscelli, A. B. (2002) · Oncogene · doi:10.1038/sj.onc.1206054 · Cited by 42
PCDH10 Interacts With hTERT and Negatively Regulates Telomerase Activity
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Prostate tumor-initiating cells: A new target for telomerase inhibition therapy?
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“active in proliferating cells of the skin, gastrointestinal system and blood [36-38].”
BackgroundSelf-citationQuantitative analysis of hTERT mRNA expression in colorectal cancer
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“Telomerase activity can be detected in some nonneoplastic tissues but is much higher in malignant tumors”
BackgroundGlioblastoma induces vascular endothelial cells to express telomerase in vitro.
Falchetti, M. L., Pierconti, F., Casalbore, P., Maggiano, N., Levi, A., Larocca, L. M., & D, R. P. M. (2003) · PubMed · Cited by 41
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“Telomerase activity can be up-regulated in vitro following activation of lymphocytes with mitogen and stimulation of T lymphocytes through TCR/CD3 complex (Hiyama et al, 1995; Igarashi & Sakaguchi, 1996; Bodnar et al, 1996).”
BackgroundInfluentialTelomerase activity in peripheral blood for diagnosis of hepatoma
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“Activation of telomerase at a site, which is normally telomerase negative, indicates the presence of immortal or malignant cells (Hiyama et al, 1995; Sommerfield et al, 1996).”
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“Only specialized subpopulations of transit amplifying stem/ progenitor cells are capable of transient telomerase expression post-development [1,13].”
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Schaetzlein, S., & Rudolph, K. L. (2004) · Reproduction Fertility and Development · doi:10.1071/rd04112 · Cited by 38
Telomerase activity in oral and maxillofacial tumors
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Stable telomere length and telomerase expression from naıve to memory B-lymphocyte differentiation
Son, N. H., Joyce, B. R., Hieatt, A., Chrest, F. J., Yanovski, J. A., & Weng, N. (2003) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(03)00018-6 · Cited by 38
Roelofs, H., de Pauw, E. S. D., Zwinderman, A. H., Opdam, S. M., Willemze, R., Tanke, H. J., & Fibbe, W. E. (2002) · Blood · doi:10.1182/blood-2002-06-1832 · Cited by 38
Hoffmann, J., & Spyridopoulos, I. (2011) · Future Cardiology · doi:10.2217/fca.11.55 · Cited by 36
“T cells upregulate telomerase activity after mitogenic stimulation [94–96].”
BackgroundTelomere uncapping during in vitro T‐lymphocyte senescence
Chebel, A., Bauwens, S., Gerland, L., Belleville, A., Urbanowicz, I., de Climens, A. R., Tourneur, Y., Chien, W. W., Catallo, R., Salles, G. A., et al. (2008) · Aging Cell · doi:10.1111/j.1474-9726.2008.00448.x · Cited by 39
Chbab, N., Egerer, A., Veiga, I. B., Jarosinski, K. W., & Osterrieder, N. (2010) · Veterinary Research · doi:10.1051/vetres/2010026 · Cited by 37
“Telomerase activity is not detectable in normal somatic cells, but is strongly expressed during fetal development and constitutively expressed in highly proliferative cells such as germ line cells, stem cells, and lymphocytes [11, 38].”
BackgroundThe correlation of TERT expression with c-myc expression in cervical cancer
Sagawa, Y., Nishi, H., Isaka, K., Fujito, A., & Takayama, M. (2001) · Cancer Letters · doi:10.1016/s0304-3835(01)00501-8 · Cited by 37
Detection of malignant effusions: Comparison of a telomerase assay and cytologic examination
Braunschweig, R., Yan, P., Guilleret, I., Delacrétaz, F., Bosman, F. T., Mihaescu, A., & Benhattar, J. (2001) · Diagnostic Cytopathology · doi:10.1002/1097-0339(200103)24:3 · Cited by 35
Telomerase and hallmarks of cancer: An intricate interplay governing cancer cell evolution
Kumar, N., & Sethi, G. (2023) · Cancer Letters · doi:10.1016/j.canlet.2023.216459 · Cited by 35
Bovine telomere dynamics and the association between telomere length and productive lifespan
Seeker, L. A., Ilska, J. J., Psifidi, A., Wilbourn, R. V., Underwood, S., Fairlie, J., Holland, R., Froy, H., Salvo‐Chirnside, E., Bagnall, A., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-31185-z · Cited by 40
Tarhan, E. F., Vural, F., Kosova, B., Aksu, K., Çoğulu, Ö., Keser, G., Gündüz, C., Tombuloğlu, M., Öder, G., Karaca, E., et al. (2007) · Rheumatology International · doi:10.1007/s00296-007-0472-9 · Cited by 36
“ever, telomerase activation also occurs in non-diseased cells, including stem cells, germline cells and lymphocytes [1, 5].”
BackgroundTelomere length of cord blood-derived CD34+ progenitors predicts erythroid proliferative potential
Schuller, C. E., Jankowski, K., & MacKenzie, K. L. (2007) · Leukemia · doi:10.1038/sj.leu.2404631 · Cited by 36
Kojima, H., Miyazaki, H., Shiwa, M., Tanaka, Y., & Moriyama, H. (2001) · The Laryngoscope · doi:10.1097/00005537-200105000-00021 · Cited by 35
Cell proliferation, carcinogenesis and diverse mechanisms of telomerase regulation
Krupp, G., Klapper, W., & Parwaresch, R. M. (2000) · Cellular and Molecular Life Sciences · doi:10.1007/pl00000708 · Cited by 36
Telomerase activity in human gynaecological malignancies.
Gorham, H. C., Yoshida, K., Sugino, T., Marsh, G., Manek, S., Charnock, M., Tarin, D., & Steve Goodison, B. (1997) · Journal of Clinical Pathology · doi:10.1136/jcp.50.6.501 · Cited by 36
Telomerase and the Benign and Malignant Megakaryoblastic Leukemias of Down Syndrome
Holt, S. E., Brown, E., & Zipursky, A. (2002) · Journal of Pediatric Hematology/Oncology · doi:10.1097/00043426-200201000-00005 · Cited by 36
Ogoshi, M., Le, T., Shay, J. W., & Taylor, R. S. (1998) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.1998.00180.x · Cited by 36
Self-citation
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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