Shortened telomere length is demonstrated in T-cell subsets together with a pronounced increased telomerase activity in CD4 positive T cells from blood of patients with mycosis fungoides and parapsoriasis

We have recently demonstrated that telomerase activity is increased and telomere length shortened in lymphocytes from peripheral blood of patients with cutaneous T-cell lymphoma. In order to determine which cell type has increased telomerase activity and shortened telomere length, CD4+, CD8+, CLA+ CD3+ and CLA- CD3+ T cells were isolated from peripheral blood of 25 patients, including 15 patients with mycosis fungoides and 10 patients with parapsoriasis. Eleven healthy individuals were used as controls; CD19+ B cells were separated from each individual as an internal control. The results showed that the increased telomerase activity was significantly predominating in the CD4+ T-cell subset. Significantly shortened telomere length was found in CD4+ and CD8+ T-cell subsets from the patients compared with the same cell subsets obtained from healthy individuals. However, no difference was observed between the subsets; CD19+ B cells collected from patients and healthy control individuals had similar telomerase activity and telomere length which was significantly different from the values found in T cells. The telomere length was significantly shorter in CLA+ CD3+ subset than in CLA- CD3+ subset. Interestingly, increased telomerase activity and shortened telomere length was also detected in CD4+ T cells from patients with parapsoriasis indicating that alteration of telomerase activity and telomere length in CD4+ T cells is an early event in the pathogenesis of cutaneous T-cell lymphoma. Thus, the results indicate that a significant high level of telomerase activity and shortened telomere length frequently occur in T cells of patients with CTCL and may reflect tumorigenesis.     

Mediation Effect of Platelet Traits on Associations of Central Obesity with Aging Biomarkers in Rural Adults of Henan,China

Background: To assess the associations of platelet traits and obesity indices with aging biomarkers (telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN)). Methods: A cross-sectional study was performed among 5091 rural Chinese adults. Obesity indices (waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR)) and platelet traits (plateletcrit (PCT), platelet large cell ratio (P-LCR), mean platelet volume (MPV) and platelet distribution width (PDW)) were collected by physical examination. The aging biomarkers were determined by quantitative real-time polymerase chain reaction. Generalized linear regression models and mediation analysis were applied to explore the relationships between platelet traits, obesity indices, and aging biomarkers. Results: The mean age of the participants was 56 years (range: 18–79). Each one-unit increment in WC, WHR and WHtR were related to a 0.316 (95% confidence interval (CI): −0.437, −0.196), 0.323 (95% CI: −0.513, −0.134) and 0.277 (95% CI: −0.400, −0.153) decrease in relative TL; or a 0.102 (95% CI: −0.197, −0.007), 0.109 (95% CI: −0.258, −0.041) and 0.101 (95% CI: −0.199, −0.004) decrease in relative mtDNA-CN. The proportions of obesity indices with aging biomarkers mediated by platelet indices ranged from 2.85% to 10.10%. Conclusions: Increased central obesity indices in relation to shortened relative TL or decreased mtDNA-CN were mediated by platelet traits, indicating that obesity in association with the accelerated aging process may be partially attributable to abnormal platelet activity.     

实验性口腔癌的端粒行为异常研究

目的：探讨ＤＭＢＡ诱导金黄地鼠颊囊癌变过程中端粒长度动态变化。方法：Ｙｏｕｔｈｅｒｎ杂交技术分析金黄地鼠颊囊癌变组织端粒ＤＮＡ序列长度。结果：金黄地鼠颊囊癌变过程中,癌变侧颊囊粘膜组织端粒长度较自身正常对照侧明显缩短,尤以诱癌后期缩短速率最快。结论：端粒长度缩短在癌变早期显著。     

Clinical Applications and Utility of a Precision Medicine Approach for Patients With Unexplained Cytopenias

ObjectiveTo demonstrate experience and feasibility of a precision medicine approach for patients with unexplained cytopenias, defined as low blood counts in one or more cell lineages, persistent for 6 months or longer, in the absence of known nutritional, autoimmune, infectious, toxic, and neoplastic (secondary) causes.Patients and MethodsPatients were evaluated in our clinic between November 8, 2016, and January 12, 2018. After a thorough evaluation of known causes, family history, and appropriate clinical assays, genomic evaluation was performed in a stepwise manner, through Sanger, targeted, and/or whole-exome sequencing. Variants were analyzed and discussed in a genomics tumor board attended by clinicians, bioinformaticians, and molecular biologists.ResultsSixty-eight patients were evaluated in our clinic. After genomic interrogation, they were classified into inherited bone marrow failure syndromes (IBMFS) (n=24, 35%), cytopenias without a known clinical syndrome which included idiopathic and clonal cytopenias of undetermined significance (CCUS) (n=30, 44%), and patients who did not fit into the above two categories (“others,” n=14, 21%). A significant family history was found in only 17 (25%) patients (9 IBMFS, 2 CCUS, and 6 others), whereas gene variants were found in 43 (63%) patients (34 [79%] pathogenic including 12 IBMFS, 17 CCUS, and 5 others]. Genomic assessment resulted in a change in clinical management in 17 (25%) patients, as evidenced by changes in decisions with regards to therapeutic interventions (n=8, 47%), donor choice (n=6, 35%), and/or choice of conditioning regimen for hematopoietic stem cell transplantation (n=8, 47%).ConclusionWe show clinical utility of a real-world algorithmic precision medicine approach for unexplained cytopenias.     

Shortened telomere length and increased telomerase activity in hamster pancreatic duct adenocarcinomas and cell lines

Recently, shortened telomere length and increased telomerase activity have been demonstrated in various human cancers. In the study reported here, we ascertained whether gene changes are characteristic of pancreatic cancers. Hamster duct carcinomas and cell lines were investigated by Southern blot analysis for telomere restriction fragment (TRF) length and by the telomeric repeat amplification protocol (TRAP) assay for telomerase activity. Comparison with normal pancreas and spleen revealed shortened TRF length and markedly increased telomerase activity in primary pancreatic duct carcinomas induced by the rapid-production model as well as in a transplantable carcinoma and the cell lines. The enzyme level was 86.0–215.7 times the low levels found in control pancreas and spleen tissues. Late-passage Syrian hamster embryo cells, known to be immortalized and tumorigenic, had shorter TRFs than the original cells in primary culture did. These results indicate that hamster pancreatic duct carcinoma cells are immortalized, with the potential for proliferation ad infinitum, and provide a model for basic therapeutic research into the substances targeting telomerase. Mol. Carcinog. 18:153–159, 1997. © 1997 Wiley-Liss, Inc.     

Wiedemann‐Rautenstrauch (neonatal progeroid) syndrome: New case with normal telomere length in skin fibroblasts

Wiedemann‐Rautenstrauch (neonatal progeroid) syndrome is an autosomal recessive condition with characteristic appearance of premature aging present at birth (aged face, natal teeth, and wrinkled skin). Other features of the syndrome are generalized lipoatrophy with specific fat accumulation in the lateral suprabuttock region, hypotrichosis, macrocephaly (pseudohydrocephalus), and mental retardation. We report on a new case that demonstrates all typical features of the syndrome. The girl is now 16 years and 10 months old and has had follow‐up from birth. We measured terminal restriction fragment (TRF) length to evaluate whether the patient's premature aging process is accompanied by shortening of telomere length in her cultured fibroblasts. Mean TRF of 13.5 kb found in our patient's fibroblasts is not shortened as compared to that of normal fibroblasts. Our results differ from those observed in Hutchinson‐Gilford progeria. © 2001 Wiley‐Liss, Inc.     

检测端粒酶活性的PCR—ELISA方法的建立

建立一种更为敏感，特异的端粒酶检测方法。方法将分子生物学和免疫学方法有机地结合起来，建立ＰＣＲ－ＥＬＩＳＡ方法并检测多种肿瘤细胞株和部分组织中端粒酶活性。结论ＰＣＲ－ＥＬＩＳＡ方法检测端粒酶活性是一种简便，快速，无放射性污染的方法，适用于肿瘤早期诊断和普查。     

Study of abnormal length of chromosomal telomere in patients with lung cancer

Telomere is the tenonal sthetUxe of the chtDInosomes Of eukaryote and it consists of repeated seqUences ofoligonucledde wb rich G[IJ. In hUInan being, the avemp length of telomere is 8 -- 14 kb and its core sc.thence is 5' mGGG3I[2'3]. Telomere and its binding...Pmtein ~ntam the stability of .hmmosome.[']. odiousstudies reported that telomere length was obviously shortened in Patients with chIDnic myeloid leukenda and solidc~inomas such as colon c~inolna and ~ c~inomalsJ. There aught b…     

Telomere length and risk of Parkinson's disease

We investigated whether telomere length was associated with the risk of Parkinson's disease (PD) in a case‐control study (96 cases and 172 age‐matched controls) nested within the Health Professionals Follow‐up Study. Relative ratio of telomere repeat copy number to single‐gene copy number in peripheral blood leukocytes was determined by quantitative real time PCR. Men with shorter telomeres had a lower PD risk (multivariate adjusted relative risk for the lowest vs. the highest quartile 0.33; 95% confidence interval: 0.12–0.90). Our results suggest that, contrary to telomere attrition observed in several aging‐related diseases, shorter telomeres are not associated with an increased risk of PD. © 2007 Movement Disorder Society     

From bad to worse: when lung cancer complicates idiopathic pulmonary fibrosis

Patients with idiopathic pulmonary fibrosis have a significantly increased risk for the development of lung cancer. The morbidity and mortality of this disease combination are substantial, and, unfortunately, there are currently few data to help guide clinicians in its diagnosis and treatment. In a recent issue of this journal, Hwang et al presented one of the first studies to evaluate lung cancer in patients with idiopathic pulmonary fibrosis at the molecular level. They demonstrate variants in regulators of the cell cycle, which are known to be important in malignant transformation and may also be important in the pathogenesis of idiopathic pulmonary fibrosis. Further understanding of the pathogenic overlap between lung cancer and idiopathic pulmonary fibrosis could help point the direction to specific diagnostic modalities and targeted treatment of both conditions in the future. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.