scholarly journals The telomere length of gastric mucosal samples and peripheral blood lymphocytes in patients who have undergone Billroth II distal gastrectomy

2020 ◽  
Vol 16 (3) ◽  
pp. 577-583
Author(s):  
Muge Ustaoglu ◽  
Ahmet Bektas ◽  
Abdulkerim Bedir ◽  
Tulay Bakir ◽  
Aynur Duzgun ◽  
...  
Keyword(s):  
Telomere Length ◽  
Peripheral Blood ◽  
Distal Gastrectomy ◽  
Peripheral Blood Lymphocytes ◽  
Billroth Ii ◽  
Blood Lymphocytes

Telomeric Recombination in Lymphocytes Implicates ALT, an Alternative Mechanism for Telomere Length Maintenance, in Normal Human Hematopoietic Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1332-1332
Author(s):  
Rodrigo T. Calado ◽  
Solomon A. Graf ◽  
Neal S. Young
Keyword(s):  
Telomere Length ◽  
Sister Chromatid ◽  
Hela Cells ◽  
Peripheral Blood ◽  
Sister Chromatid Exchange ◽  
Mammalian Cells ◽  
K562 Cells ◽  
Peripheral Blood Lymphocytes ◽  
Blood Lymphocytes ◽  
Telomeric Probe

Abstract Telomeres are the very ends of chromosomes and protect the genome from recombination, end-to-end-fusion, and recognition as damaged DNA. Telomeres are eroded with each cell division, eventually reaching such critically short length as to cause cell cycle arrest, apoptosis, or genomic instability. In most highly proliferative cells, including hematopoietic stem cells and T lymphocytes, telomere attrition is countered by telomere extension by telomerase reverse transcriptase complex. The majority of cancer cells also express telomerase, which maintains telomere length and allows indefinite cell proliferation. However, about 10% of tumors maintain telomere length in the absence of telomerase by mechanisms collectively termed alternative lengthening of telomeres (ALT). ALT mainly acts through asymmetrical exchange of telomeric material between chromosomes or sister chromatids, producing one daughter-cell with short telomeres and a limited life-span and its sister with long telomeres and higher proliferative capacity. To date, ALT has only been reported in cancer cells or through genetic engineering of mammalian cells. Here we investigated whether ALT mechanisms were active in hematopoietic cells using chromosome orientation fluorescent in situ hybridization (CO-FISH). In standard FISH, a telomeric probe produces fours signals per chromosome, one at each end of the two chromatids. Using CO-FISH, the newly synthesized DNA strand is fragmented by BrdU incorporation and UV light exposure and then digested by exonucleases. In CO-FISH, a telomeric probe produces two signals only, one at each end of the chromosome; in the presence of telomeric recombination, the telomeric signal is split, generating more than two signals per chromosome. Peripheral blood lymphocytes from three healthy volunteers, normal human fibroblasts, K562 cells, telomerase-positive HeLa cells (known to be negative for ALT),and telomerase-negative VA13 cells (known to be positive for ALT) were investigated for telomeric sister chromatid exchange (t-SCE); at least 20 metaphases per cell type were examined. Cultured peripheral blood lymphocytes and VA13 cells both showed increased levels of telomeric sister chromatid exchange in comparison to the other cells (P=0.0001): telomeric probe generated 2.62±0.11 telomeric signals/chromosome in lymphocytes; 2.23±0.04 in VA13 cells; 2.09±0.01 in HeLa cells; 2.02±0.01 in K562 cells; and 2.02±0.01 in human skin fibroblasts. Staining incorporated-BrdU over 24 hours and evaluation of “harlequin” chromosomes point to a similar rate of genomic sister chromatid exchange in lymphocytes, VA13 cells, and HeLa cells, suggesting that high chromatid exchange is confined to the telomeric region. A physical association between promyelocytic leukemia protein (PML) and telomeres is characteristic of some ALT-positive cells, but confocal microscopy failed to co-localize the telomeric probe and anti-PML monoclonal antibody in peripheral blood lymphocytes, suggesting that t-SCE in lymphocytes is not mediated by PML. This is the first demonstration of ALT activation in normal mammalian cells. ALT may be activated in peripheral blood lymphocytes as a complementary mechanism to maintain telomere length, and may explain the differences in age-related telomere shortening observed between lymphocytes and granulocytes.

scholarly journals Telomere Length in Peripheral Blood Lymphocytes Contributes to the Development of HPV-Associated Oropharyngeal Carcinoma

2013 ◽  
Vol 73 (19) ◽  
pp. 5996-6003 ◽  
Author(s):  
Yang Zhang ◽  
Erich M. Sturgis ◽  
Kristina R. Dahlstrom ◽  
Juyi Wen ◽  
Hongliang Liu ◽  
...  
Keyword(s):  
Telomere Length ◽  
Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Oropharyngeal Carcinoma ◽  
Blood Lymphocytes

scholarly journals Is telomere length in peripheral blood lymphocytes correlated with cancer susceptibility or radiosensitivity?

2007 ◽  
Vol 97 (12) ◽  
pp. 1696-1700 ◽  
Author(s):  
J Barwell ◽  
L Pangon ◽  
A Georgiou ◽  
Z Docherty ◽  
I Kesterton ◽  
...  
Keyword(s):  
Telomere Length ◽  
Peripheral Blood ◽  
Cancer Susceptibility ◽  
Peripheral Blood Lymphocytes ◽  
Blood Lymphocytes

scholarly journals Chromosomal damage and telomere length in peripheral blood lymphocytes of cancer patients

2020 ◽  
Author(s):  
Sona Vodenkova ◽  
Michal Kroupa ◽  
Zdenka Polivkova ◽  
Ludovit Musak ◽  
Miloslav Ambrus ◽  
...  
Keyword(s):  
Telomere Length ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Chromosomal Damage ◽  
Blood Lymphocytes

Screening of Telomere Length in Peripheral Blood Lymphocytes From Patients with Aplastic Anemia by Flow-Fluorescence in Situ Hybridization.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3205-3205
Author(s):  
Nobuhiro Nishio ◽  
Yoshiyuki Takahashi ◽  
Hideki Muramatsu ◽  
Asahito Hama ◽  
Toshihito Nagata ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Telomere Length ◽  
Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Telomere Shortening ◽  
Blood Lymphocytes ◽  
Normal Individuals ◽  
Telomere Signal ◽  
Normal Controls

Abstract Abstract 3205 Poster Board III-142 Telomeres in peripheral blood cells from patients with aplastic anemia (AA) are shorter than those from normal individuals. One possible explanation is that telomere shortening reflects the extent and duration of damage to hematopoietic stem cells and the number of compensatory stem cell divisions. Patients with such stressed hematopoiesis probably do not respond to immunosuppressive therapy (IST). Cryptic forms of dyskeratosis congenita (DC) have been recognized in patients with AA who do not have physical abnormalities, but who harbor the gene mutation associated with telomere maintenance. To identify such patients is important because those who have these mutations might respond poorly to IST. The present study evaluates the usefulness of screening telomere length in peripheral blood lymphocytes from patients at the time of diagnosis with AA by flow-fluorescence in situ hybridization (flow-FISH) using Telomere PNA kits (Dako Cytomation, Glostrup, Denmark). After gating diploid cells based on propidium iodine staining, lymphocytes were isolated according to size and granularity. Relative telomere length (RTL) was calculated as the ratio between the telomere signal of each sample and the telomere signal of the control cell line. Because telomeres shorten with age, we obtained age-adjusted measurements for comparison. We used flow-FISH to measure the length of telomeres in peripheral blood lymphocytes from five and two patients with classical and cryptic DC who had the TERT mutation, respectively, to determine whether these two forms of DC can be screened. Significant telomere shortening was detected in all seven patients compared with age-matched normal individuals. To determine the association between telomere length and response to IST, we compared telomere lengths in peripheral blood lymphocytes from 61 normal controls and 27 patients with AA (very severe, severe and non-severe, n = 9 each) at diagnosis who received IST with antithymocyte globulin (ATG) and cyclosporine. The median age of the patients was 9.0 years (range, 1.5 to 14.8). The causes of AA were unknown etiology in 25 patients and hepatitis in 2. In total, 17 of the 27 patients (63%) responded to IST at 6 months after administration of ATG. Age-adjusted delta RTLs did not significantly differ between normal controls and responders (p = 0.181), but those in non-responders were significantly lower than those in normal individuals (p = 0.000). Our findings suggest that screening telomere length in patients with AA at diagnosis is useful for detecting cryptic DC and for predicting responses to IST. Disclosures No relevant conflicts of interest to declare.

The Telomere Length In Peripheral Blood Lymphocytes Is a Useful Predictor of the Response to Immunosuppressive Therapy In Patients with Acquired Aplastic Anemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2042-2042
Author(s):  
Yoshiyuki Takahashi ◽  
Sayoko Doisaki ◽  
Nobuhiro Nishio ◽  
Hideki Muramatsu ◽  
Akira Shimada ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Immunosuppressive Therapy ◽  
Telomere Length ◽  
Peripheral Blood ◽  
Univariate Analysis ◽  
Peripheral Blood Lymphocytes ◽  
Telomere Maintenance ◽  
Blood Lymphocytes ◽  
Diploid Cells ◽  
Telomere Signal

Abstract Abstract 2042 Introduction: The ability to predict the response to immunosuppressive therapy (IST) in patients with aplastic anemia (AA) will avoid unnecessary and possibly harmful treatment. To this end, several in vitro tests have been proposed as useful predictors of response in adult patients. However, we previously reported that the presence of either human leukocyte antigen (HLA)-DR15, a minor population of paroxysmal nocturnal hemoglobinuria (PNH)-type cells, or of autoantibodies to postmeiotic segregation increased 1 (PMS1) in children with AA, were not useful predictors of the response to IST, suggesting a different etiology of AA between adults and children (Yoshida, N et al Br J Haematol. 2008). Telomeres in peripheral blood cells from AA patients are shorter than those from normal individuals in 30% of patients. This shorter telomere length in AA patients is thought to result from genetic abnormalities in the genes related to telomere maintenance, stressed hematopoiesis due to immunological attack, and increased cell division. An NIH group and we reported that cryptic forms of dyskeratosis congenita (DC) are present in just under 5% of patients with AA who do not have physical abnormalities, but who harbour the gene mutation associated with telomere maintenance (Yamaguchi, H et al. N Engl J Med. 2005, Liang, J et al. Haematologica 2006). To identify such patients is important because those who have these mutations might respond poorly to IST. However, the presence of cryptic forms of DC does not explain the causes of short telomeres in the other patients. We hypothesized that patients with short telomeres may respond poorly to IST, and thus evaluated the relationship between telomere length in hematopoietic cells before IST and the response to IST in patients with AA. Patients and Methods: We enrolled 40 newly diagnosed children with AA (median age, 10 years; range, 1 to 16 years) who received IST. We obtained peripheral blood lymphocytes from the patients with AA at the time of diagnosis and prospectively measured the telomere length of lymphocytes prior to IST by flow-fluorescence in situ hybridization (flow-FISH) using Telomere PNA kits (Dako Cytomation, Glostrup, Denmark). After gating diploid cells based on propidium iodine staining, lymphocytes were isolated according to size and granularity. Relative telomere length (RTL) was calculated as the ratio between the telomere signal of each sample and the telomere signal of the control cell line. Because telomeres shorten with age, we obtained age-adjusted measurements for comparison from 71 normal age-matched individuals. Delta RTL of each patient with AA was calculated using the distance of the RTL from the line of age-adjusted normal telomere length. Results: Of the 40 patients, at diagnosis AA was very severe in 12, severe in 13, and non-severe in 15. All received IST with horse antithymocyte globulin (ATG) and cyclosporine. The causes of AA were idiopathic in 38 patients and hepatitis in 2. In total, 25 of the 40 patients (63%) responded to IST at 6 months after administration of ATG. Between the responder and non-responder groups, no significant differences in gender, age, etiology, disease severity or interval from diagnosis, and IST were observed. Univariate analysis for IST response did not find any significant differences in median WBC count, neutrophil count, Hb level, reticulocyte count, platelet count or minor PNH clone positivity between the groups. However, delta RTL was significantly lower in non-responders than in responders (p=0.035). Multivariate analysis for response to IST revealed that only delta RTL was significantly lower in non-responders than responders (p = 0.049). Conclusion: The telomere length in lymphocytes is promising not only to identify cryptic DC but also to predict the response to IST of patients with AA. A further larger analysis is warranted to evaluate the correlation between telomere length and the response to IST in AA patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Telomere length in peripheral blood lymphocytes related to genetic variation in telomerase, prognosis and clinicopathological features in breast cancer patients

Mutagenesis ◽  
2020 ◽  
Author(s):  
Michal Kroupa ◽  
Sivaramakrishna Rachakonda ◽  
Veronika Vymetalkova ◽  
Kristyna Tomasova ◽  
Vaclav Liska ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Telomere Length ◽  
Peripheral Blood ◽  
Quantitative Polymerase Chain Reaction ◽  
Peripheral Blood Lymphocytes ◽  
Clinicopathological Features ◽  
Genome Wide Association Studies ◽  
Healthy Controls ◽  
Blood Lymphocytes ◽  
Potential Biomarker

Abstract Disruption of telomere length (TL) homeostasis in peripheral blood lymphocytes has been previously assessed as a potential biomarker of breast cancer (BC) risk. The present study addressed the relationship between lymphocyte TL (LTL), prognosis and clinicopathological features in the BC patients since these associations are insufficiently explored at present. LTL was measured in 611 BC patients and 154 healthy controls using the monochrome multiplex quantitative Polymerase Chain Reaction assay. In addition, we genotyped nine TL-associated single-nucleotide polymorphisms that had been identified through genome-wide association studies. Our results showed that the patients had significantly (P = 0.001, Mann–Whitney U-test) longer LTL [median (interquartile range); 1.48 (1.22–1.78)] than the healthy controls [1.27 (0.97–1.82)]. Patients homozygous (CC) for the common allele of hTERT rs2736108 or the variant allele (CC) of hTERC rs16847897 had longer LTL. The latter association remained statistically significant in the recessive genetic model after the Bonferroni correction (P = 0.004, Wilcoxon two-sample test). We observed no association between LTL and overall survival or relapse-free survival of the patients. LTL did not correlate with cancer staging based on Union for International Cancer Control (UICC), The tumor node metastasis (TNM) staging system classification, tumour grade or molecular BC subtypes. Overall, we observed an association between long LTL and BC disease and an association of the hTERC rs16847897 CC genotype with increased LTL. However, no association between LTL, clinicopathological features and survival of the patients was found.

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