Original Article
Mutations in TERT, the Gene for Telomerase Reverse Transcriptase, in Aplastic Anemia
N Engl J Med 2005; 352:1413-1424April 7, 2005
- Abstract
Background
Mutations in TERC, the gene for the RNA component of telomerase, cause short telomeres in congenital aplastic anemia and in some cases of apparently acquired hematopoietic failure. We investigated whether mutations in genes for other components of telomerase also occur in aplastic anemia.
Methods
We screened blood or marrow cells from 124 patients with apparently acquired aplastic anemia and 282 control subjects for sequence variations in the TERT, DKC1, NHP2, and NOP10 genes; an additional 81 patients and 246 controls were examined for genetic variations in TERT. Telomere lengths and the telomerase activity of peripheral-blood leukocytes were evaluated in patients carrying genetic variants. Identified mutations were transfected into telomerase-deficient cell lines to examine their effects and their mechanism of action on telomerase function.
Results
Five heterozygous, nonsynonymous mutations (which cause an amino acid change in the corresponding protein) were identified in TERT, the gene for the telomerase reverse transcriptase catalytic enzyme, among seven unrelated patients. Leukocytes from these patients had short telomeres and low telomerase enzymatic activity. In three of these patients, the mutation was also detected in buccal mucosa cells. Family members carrying the mutations also had short telomeres and reduced telomerase activity but no evident hematologic abnormality. The results of coexpression of wild-type TERT and TERT with aplastic anemia–associated mutations in a telomerase-deficient cell line suggested that haploinsufficiency was the mechanism of telomere shortening due to TERT mutations.
Conclusions
Heterozygous mutations in the TERT gene impair telomerase activity by haploinsufficiency and may be risk factors for marrow failure.
Media in This Article
Figure 1
TERT Mutations in Aplastic Anemia.Figure 2
Functional Analysis of TERT Mutations.Article Activity
- Article
In aplastic anemia, the bone marrow contains very few hematopoietic cells and consists mainly of fat. The disease can be acquired or constitutional.1 In most acquired cases, the hematopoietic tissue is the target of an immune process dominated by oligoclonal expansion of type I cytotoxic T cells, which secrete interferon-γ and tumor necrosis factor α and cause hematopoietic cell death by apoptosis.2,3 Acquired aplastic anemia can be successfully treated by allogeneic bone marrow transplantation or immunosuppressive therapy.4
Fanconi's anemia and dyskeratosis congenita are the most common types of constitutional (congenital) aplastic anemia.5 X-linked dyskeratosis congenita (Online Mendelian Inheritance in Man [OMIM] number 305000) is caused by mutations in the DKC1 gene, which encodes dyskerin, a small nucleolar ribonucleoprotein particle that associates with the telomerase complex.6,7 Involvement of this gene has implicated the telomere-repair complex in the pathophysiology of dyskeratosis congenita8-11; indeed, cells from patients with this disease have strikingly short telomeres and low telomerase activity.8 Subsequently, mutations in the TERC gene, which encodes the RNA component of the telomerase complex, were identified in the autosomal dominant form of dyskeratosis congenita (OMIM number 127550).9,12
Telomeres are structural elements that seal the ends of chromosomes, protecting them from recombination, end-to-end fusion, and recognition as damaged DNA. In human somatic cells, telomeres typically consist of more than 1000 tandem repeats of nucleotides (CCCTAA in one strand of DNA and TTAGGG in the other) and associated proteins. These repeats are gradually lost with cellular replication and aging, owing to the inability of DNA polymerase to fully replicate the 3' end of DNA.13,14 The attrition of repeats eventually shortens telomeres critically; the result is arrested proliferation and senescence, shortened life span, apoptosis, or genomic instability of the cell.15 Maintenance of the integrity of telomeres requires the telomerase ribonucleoprotein complex, which consists of telomerase reverse transcriptase (TERT) and its integral RNA template (TERC), in addition to other proteins.14,16 TERT copies a short region of TERC into telomeric DNA to extend the 3' end of the chromosome.14,17-19
We and others have found short telomeres in leukocytes from approximately one third of patients with acquired aplastic anemia, especially those who do not have a response to immunosuppressive therapy.20,21 For this reason, we sought evidence of cryptic dyskeratosis congenita and TERC mutations in aplastic anemia.22-25 We discovered two families in which each proband had apparently acquired aplastic anemia. TERC mutations were present in the severely affected patients and multiple other family members, but physical stigmata of dyskeratosis congenita (abnormal skin pigmentation, nail dystrophy, and mucosal leukoplakia) were absent.24 Nevertheless, because TERC mutations are infrequent in acquired aplastic anemia,23,25 we hypothesized that mutations in genes corresponding to other components of the telomerase ribonucleoprotein complex could contribute to bone marrow failure.
Methods
Patients and Controls
Blood samples were obtained from 205 unrelated patients with apparently acquired aplastic anemia (age range, 2 to 83 years; median, 34) who were treated at a single institution (the Hematology Branch of the National Heart, Lung, and Blood Institute, National Institutes of Health). The diagnosis of aplastic anemia was based on the bone marrow and blood-count criteria of the International Agranulocytosis and Aplastic Anemia Study.26 The first group, consisting of 124 patients, was selected for study on the basis of one of the following: a lack of response to immunosuppressive therapy, a family history of hematologic abnormalities without physical anomalies characteristic of dyskeratosis congenita, or short telomeres in leukocytes, as previously observed.21 The second group consisted of 81 consecutive patients seen in the same clinic from January 2004 to July 2004 for evaluation and treatment of acquired aplastic anemia.
Of the 205 patients, 98 were female and 107 were male. Race or ethnic background, as reported by the patients or their guardians, was as follows: white, 137 patients (67 percent); black, 23 (11 percent); Hispanic, 29 (14 percent); Asian, 14 (7 percent); and Amerindian, 2 (1 percent). Patients came from the United States and from several Latin-American and Asian countries. Carriers of a TERC mutation were excluded from analysis. Patients or their guardians provided written informed consent for genetic testing, according to protocols approved by the institutional review board of the National Heart, Lung, and Blood Institute.
Samples from 282 healthy persons were studied as controls: 117 were white (94 from Human Variation Panel HD100CAU, Coriell Cell Repositories [http://locus.umdnj.edu/nigms/cells/humdiv.html], and 23 from SNP500Cancer [http://snp500cancer.nci.nih.gov]), 118 black (94 from Human Variation Panel HD100AA and 24 from SNP500Cancer), 23 Hispanic (from SNP500Cancer), and 24 Asian (from SNP500Cancer).27 The SNP500Cancer project aims to resequence reference samples from four ethnically diverse groups with the use of anonymous samples from the Coriell Cell Repositories in order “to validate known or newly discovered single nucleotide polymorphisms . . . and other important classes of genetic variants of potential importance to molecular epidemiology studies of cancer and other diseases.”27 Samples from an additional 246 anonymous healthy subjects of Hispanic origin (52 percent Peruvians, 28 percent Latin Americans, and 20 percent Pima and Maya Amerindians) were also examined as controls. In total, 1056 chromosomes from four major ethnic groups constituted the control group.
Mutational Analysis
Polymerase-chain-reaction (PCR) amplification of genes encoding the telomerase complex — namely, DKC1, NOP10, NHP2, and TERT — was performed with DNA samples extracted from peripheral-blood or bone marrow cells, as previously described.25 Primers and PCR conditions are listed in Table 1 of the Supplementary Appendix (available with the full text of this article at www.nejm.org). PCR products were purified with a QIAquick PCR purification kit (Qiagen), and direct sequencing was performed with BigDye Terminator version 3.1 (Applied Biosystems). Specific primers for sequencing were designed (Table 2 of the Supplementary Appendix), and sequencing products were analyzed in an automated genetic-sequence analyzer (ABI Prism 3100, Applied Biosystems). All sequences were determined in both directions, and mutations were confirmed by three separate PCR amplification products.
To assess microdeletion or microinsertion, PCR products were inserted directly into the pCR2.1-TOPO vector and transformed into competent Escherichia coli (TOP10F' strain) with a TOPO TA cloning kit (Invitrogen). Patients had previously been screened for TERC mutations, as described elsewhere,25 and those positive for mutations were excluded from analysis.
Functional Analysis
The average length of telomere repeats at chromosome ends in individual peripheral-blood leukocytes was measured by flow fluorescence in situ hybridization, as previously reported.28 The telomerase activity of activated T cells was evaluated by the telomeric-repeat amplification protocol with the TRAPeze Telomerase Detection kit (Chemicon) in cells from patients and relatives carrying mutations at codon 202 or 1090 (cells from patients carrying mutations at codon 412, 694, or 772 were not available). Peripheral-blood cells were cultured in RPMI 1640 with L-glutamine and 10 percent fetal-calf serum in the presence of phytohemagglutinin (5 μg per milliliter) and interleukin-2 (40 IU per milliliter) for four days at 37°C with 5 percent carbon dioxide. An aliquot was stained with anti-CD3 and anti-CD4–phycoerythrin (BD Biosciences) for fluorescence-activated cell-sorter analysis in an LSR II flow cytometer (BD Biosciences). Cell-cycle and DNA-ploidy analyses were performed with a NuCycl kit (Exalpha), according to the manufacturer's instructions. Protein was extracted and telomerase activity was assayed according to the manufacturer's instructions, with slight modifications, as previously described.29
Mutations were introduced into the pcI-TERT plasmid with use of the QuikChange site-directed mutagenesis kit (Stratagene) and were verified by DNA sequencing. Two micrograms of either wild-type or mutant pcI-TERT DNA was transfected into telomerase-deficient VA13+TERC cells (at 60 percent confluence), as previously described.29 VA13+TERC is a line of human-lung fibroblasts that do not express telomerase activity, owing to the absence of TERT expression; instead the cells adopt an alternative mechanism for telomere maintenance, the ALT (alternative lengthening of telomeres) pathway.30 In studies of cotransfection into VA13-TERC cells, two ratios of wild-type to mutant pcI-TERT DNA were used: 1 μg to 1 μg or 1 μg to 3 μg, respectively, which totaled 2 μg or 4 μg, respectively. Subsequent manipulations of the cell extracts were carried out as described previously.29 Mutations other than the codon 412 mutations were tested at least twice in the transfection experiments. Total cellular RNA was also extracted with Trizol reagent (Invitrogen), and TERT expression assayed by Northern blotting with the random-primed probes to the TERT coding sequence.29
Peripheral-blood mononuclear cells from mutation carriers and controls were assessed in methylcellulose medium for the number of hematopoietic progenitors with the use of recombinant cytokines (StemCell Technologies), according to the manufacturer's instructions. Myeloid and erythroid colonies were counted 10 days after triplicate sample plating.
Statistical Analysis
Differences in the frequencies of coding-sequence variations between samples from patients with aplastic anemia and those from controls were evaluated by means of Fisher's exact test. The Kruskal–Wallis nonparametric test, followed by Dunn's multiple-comparison test, was used to compare differences in the number of colonies in hematopoietic-progenitor assays.
Results
Mutations
Of the 205 patients with aplastic anemia, 5 carried a heterozygous TERC mutation and were excluded from analysis. Among the remaining 200 patients, five novel nonsynonymous mutations (i.e., mutations that introduce an amino acid change in the corresponding protein) in TERT, all heterozygous, were identified in 7 patients with apparently acquired aplastic anemia (Table 1Table 1
Mutations and Polymorphisms Resulting in Amino Acid Changes in Genes Encoding the Telomerase Complex in Patients with Acquired Aplastic Anemia. and Table 2Table 2
Clinical Characteristics and Laboratory Profiles of Patients Carrying TERT Mutations.). A mutation in codon 202, which replaced alanine with threonine in the N-terminal region of TERT (codon 202 Ala/Thr), was found in two unrelated patients; another mutation, codon 412 His/Tyr, also in the N-terminal of TERT, was identified in two other, unrelated patients. Codon 694 Val/Met and codon 772 Tyr/Cys were located within the reverse transcriptase domain, and codon 1090 Val/Met was located in the C-terminal of TERT (Figure 1AFigure 1 TERT Mutations in Aplastic Anemia. and Figure 1B). No mutations were found in DKC1, NOP10, and NHP2, but nonsynonymous, single-nucleotide polymorphisms were found in all the genes analyzed, at similar overall allele frequencies in both the patients and the controls (Table 1). Additional synonymous, single-nucleotide polymorphisms were identified in TERT and in the box H/ACA-related genes (where box H/ACA refers to RNA involved in RNA modification) (Tables 3 and 4 of the Supplementary Appendix).The germ-line origin of the TERT mutations was established by the detection of the mutations in DNA from buccal mucosa specimens obtained from three of the patients affected by aplastic anemia and in DNA from blood cells obtained from two of these patients' family members. However, none of these patients or their family members showed physical signs of dyskeratosis congenita. The bone marrow cells of all the patients carrying TERT mutations had a normal karyotype. Detailed family histories revealed hematopoietic disorders in relatives of four of the seven affected patients (Table 2).
Telomere Length
Compared with a reference group of 400 normal subjects (unpublished data), the length of telomeres in peripheral-blood leukocytes of patients carrying TERT mutations was markedly shortened (Figure 1C). In contrast, among patients with aplastic anemia with polymorphisms in the TERT gene, telomere lengths were within the 90 percent confidence interval of the normal reference group. In the family of a patient with a codon 202 Ala/Thr mutation, one of his daughters, his two brothers, and one sister also carried the same heterozygous mutation. The leukocytes of these family members had short telomeres, but to date, they have not been found to have hematologic abnormalities in the blood; the leukocytes of one daughter and one sister without the mutation had normal telomeric length (Figure 1D). Three genetic variants in TERT were considered polymorphisms because they were observed in normal donors and were not associated with telomere shortening; they included a change in codon 441 in exon 2 that resulted in the deletion of glutamine, a nonsynonymous single-nucleotide polymorphism in codon 279 Ala/Thr in exon 2, and a nonsynonymous single-nucleotide polymorphism in codon 1062 Ala/Thr in exon 15. Moreover, the observed allele frequencies for the two nonsynonymous single-nucleotide polymorphisms were similar in patients with aplastic anemia and controls (Table 1).
Telomerase Activity of Cultured Cells
Peripheral-blood mononuclear cells from patients and healthy family members carrying codon 202 Ala/Thr and codon 1090 Val/Met mutations and from healthy controls were cultured. After expansion, more than 90 percent of the cells were viable, according to a dye-exclusion assay; on flow cytometry, the cells were mainly T cells (either CD4+ or CD4–) and had similar proliferation rates, as determined by cell-cycle analysis (data not shown). Telomeric-repeat amplification analysis of cell lysates from the patients showed that telomerase activity was reduced by approximately 50 percent as compared with that of healthy, unrelated controls (Figure 2AFigure 2
Functional Analysis of TERT Mutations.).Hematopoietic Function
We measured the number of erythroid and myeloid colonies in peripheral-blood specimens from two healthy siblings of Patient A (who had the codon 202 Ala/Thr mutation; one sibling was a carrier and one a noncarrier) and from two siblings of Patient G (who had the codon 1090 Val/Met mutation; one sibling was a carrier and one a noncarrier) and in blood specimens from healthy controls. The total number of progenitors was significantly lower among carriers than among noncarriers or controls (mean [±SD] colonies, 41±9, 116±45, and 118±30, respectively; P<0.05), indicating that hematopoietic function was reduced in carriers of a TERT mutation.
Telomerase Activity of Cells Transfected with Vectors Containing a TERT Mutation
Aplastic anemia–related TERT sequence variants were created in a TERT expression vector, which was then transfected into VA13+TERC cells. As shown in Figure 2B, the aplastic anemia–associated TERT preparations showed varying degrees of deficiency in telomerase enzymatic activity in these reconstituted cells. Whereas cell lysates carrying TERT mutations in codons 202, 694, 772, and 1090 showed less than 1 percent telomerase activity as compared with lysate containing the wild-type TERT gene (lanes 1 through 15), mutation of codon 412 resulted in approximately 50 percent telomerase activity (lanes 19 through 24). Loss of enzymatic function in the transfected cells was not due to altered transcription of the mutated TERT gene or instability of the messenger RNA, since RNA expression levels were found to be similar to those in the normal, wild-type TERT sample, as determined by Northern blot analysis (Figure 2D).
Coexpression of Wild-Type and Mutation-Containing TERT Vectors
Telomerase functions as a multimeric complex consisting of at least two TERT enzyme proteins and two TERC RNA templates.31-36 Because primary cultures of cells from patients carrying TERT mutations had reduced telomerase activity, we investigated whether the reduction was due to haploinsufficiency or a dominant negative mechanism of action of the mutated TERT on the wild-type sequence. We cotransfected equal amounts of vector containing wild-type TERT and the individual mutations into VA13+TERC cells. As shown in Figure 2C, lysates from cells that were cotransfected with wild-type TERT and TERT containing codon 202 Ala/Thr, codon 694 Val/Met, codon 772 Tyr/Cys, or the codon 412 His/Tyr mutations (at either 1:1 or 1:3 ratios, based on plasmid concentration) also showed an approximately 50 percent reduction in the enzymatic activity of telomerase (lanes 28, 29, 30, 34, 35, 36, 43, 44, 45, and 49 through 54) in comparison with samples that were transfected with wild-type TERT and vectors containing either the codon 441 polymorphism (lanes 46, 47, and 48) or the control vector expressing wild-type TERT (lanes 25, 26, 27, 31, 32, 33, 40, 41, and 42). That wild-type telomerase activity was only partially reduced by mutated TERT suggested a mechanism of haploinsufficiency.
Discussion
In this study, we found nonsynonymous mutations in the TERT gene, which encodes telomerase reverse transcriptase, in patients with apparently acquired aplastic anemia. That these mutations are functionally important is indicated by their association with very short telomeres and reduced telomerase activity in primary cultures of the patients' leukocytes. In cell-culture experiments, the aplastic anemia–associated TERT mutations resulted in decreased telomerase activity by a mechanism of haploinsufficiency: that is, the remaining normal allele was insufficient for the production of adequate amounts of the enzyme.
We identified mutations in all three major domains of the TERT protein: the N- and C-terminal telomerase-specific domains and the conserved reverse-transcriptase domain.31,37-40 Primary cultures of leukocytes from patients and relatives carrying TERT mutations yielded lower telomerase enzymatic activity than did cultures of leukocytes from healthy persons. When we cotransfected vectors containing the wild-type TERT and TERT with the individual mutations into a telomerase-negative cell line, the telomerase activity of the mutated forms of the TERT proteins was only partially reduced, indicating that these mutations may act by haploinsufficiency and not by a true dominant negative mechanism. Haploinsufficiency is also the main mechanism by which dyskeratosis congenita and aplastic anemia–associated TERC mutations decrease telomerase activity.41,42 Generally, a 50 percent reduction in enzyme expression in heterozygotes does not influence the phenotype, but expression of the telomerase complex is tightly regulated, and a partial reduction in its activity is sufficient to disturb the maintenance of telomere length. In murine models, Tert is a limiting factor, and loss of one copy of mTert also results in telomere shortening intermediate between telomere lengths in wild-type and mTert-null embryonic stem cells.43
Our data are also consistent with an effect of the TERT gene deletion in patients with the cri du chat syndrome,44 in which the distal portions of chromosome 5p in one of the alleles, including the entire coding region of the TERT gene, are deleted. Reduced TERT expression and low telomerase activity have been observed in some patients with the cri du chat syndrome, suggesting haploinsufficiency as the mechanism of action in this syndrome as well. Since patients with aplastic anemia and TERT mutations do not have physical anomalies, TERT deletion alone is unlikely to be responsible for the complete phenotype of the cri du chat syndrome. That patients with this syndrome do not have marrow failure may be explained by “disease anticipation,” as occurs in dyskeratosis congenita12: in that condition, the symptoms and signs become apparent at progressively younger ages in successive generations, and telomere shortening progresses over several generations.
Published mutations in genes of the telomere-repair complex in patients with bone marrow failure are summarized in Figure 3Figure 3
Schematic Structure of the Telomere-Repair Complex and Location of Mutations Associated with Syndromes of Bone Marrow Failure.. Nucleotide alterations in the DKC1 gene and some mutations located within the 3' region of TERC in box H/ACA and the CR7 domain result in dyskeratosis congenita,9,12 with presentation of pancytopenia in the first decades of life and associated physical anomalies. Mutations in the 5' region of TERC (in the so-called pseudoknot and CR4–CR5 domains) and in TERT are more frequently associated with aplastic anemia later in life and are not usually related to the physical stigmata of dyskeratosis congenita.24,25 TERT and the 5' region of TERC are required for telomerase enzymatic activity and for assembly of the telomerase ribonucleoprotein complex, whereas the box H/ACA–related proteins (dyskerin, NOP10, and NHP2) and 3' region of TERC affect the stability of the complex and its maturation.More patients should be analyzed genetically to determine whether there is an association between phenotypic features of the disease (e.g., the severity of pancytopenia, the age at the onset of clinical manifestations, and physical anomalies) and the location of genetic lesions in specific regions of functional activity in the genes encoding the telomere repair complex. Small nucleolar RNA with the box H/ACA motif participates in pseudouridylation of ribosomal RNA and other small RNAs,45 but there are no data yet to suggest that TERC RNA or telomerase reverse transcriptase also has a role in post-transcriptional modification of ribosomal RNA.
Although the number of patients in our study is too small to allow us to draw a definite conclusion, none of the patients with TERT mutations had a response to immunosuppressive therapy. In our previous series,24,25 patients with TERC mutations also did not have an adequate response to immunosuppression. It is possible that specific mutations in one or more genes could influence the choice of therapy — the choice of specific drug regimens or the decision to undergo stem-cell transplantation. For this reason, measurements of telomere length in blood leukocytes and genetic testing for telomerase gene mutations could be useful in the management of acquired aplastic anemia.
Remarkably, humans with deficient telomerase activity, as well as telomerase knock-out mice,46-48 may appear to be phenotypically normal and have minimal or no apparent hematologic abnormalities. However, because their hematopoietic proliferative capacity is limited, affected persons and animals may be especially susceptible to environmental insults to the bone marrow (such as those caused by drugs or viruses), and patients' reduced number of stem cells may limit their response to immunosuppressive therapies. Certain histocompatibility antigens and cytokine-gene polymorphisms are more prevalent in the immune-mediated marrow failure syndromes49-52; these genetically determined immunologic characteristics affect the recognition of specific antigens and the nature of the immune response. For the hematopoietic target cells, TERC and TERT mutations provide a further genetic explanation for the rare, seemingly idiosyncratic appearance of aplastic anemia. Additional genetic variants should be sought in an effort to characterize possible modifiers of outcome and to explain differences in the timing of diagnosis as well as disease penetrance. Mutations in genes of the telomere repair complex reduce the size of the hematopoietic stem-cell compartment and the regenerative capacity of the marrow, making carriers of gene mutations susceptible to the development of marrow failure and affecting the course of aplastic anemia once it develops.
TERT and TERC mutations may be viewed as genetic risk factors for human hematopoietic failure. Defects in the maintenance of telomere length result in a reduced hematopoietic stem-cell compartment that may be especially vulnerable to environmental insults.
Drs. Yamaguchi, Calado, and Ly contributed equally to this article.
We are indebted to Drs. Brian Henderson and Larry Kolonel of the Multi-Ethnic Cohort Study for providing samples from Hispanic controls and to Ms. Olga Nunez for assisting in the care of the patients and for obtaining blood and bone marrow samples.
Source Information
From the Hematology Branch, National Heart, Lung, and Blood Institute (H.Y., R.T.C., S.K., N.S.Y.), and the Pediatric Oncology Branch, National Cancer Institute (S.J.C.), National Institutes of Health, Bethesda, Md.; the Experimental Pathology Division, Department of Pathology and Laboratory Medicine, Emory University, Atlanta (H.L.); and the Terry Fox Laboratory, BC Cancer Research Centre (G.M.B., P.M.L.), and the Department of Medicine, University of British Columbia (P.M.L.) — both in Vancouver, B.C., Canada.
Address reprint requests to Dr. Young at the Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, 10 Center Dr., Bldg. 10/CRC, Rm. 3E-5140, Bethesda, MD 20892-1202, or at youngns@mail.nih.gov.
- References
References
1
Young NS ,Maciejewski J . The pathophysiology of acquired aplastic anemia. N Engl J Med 1997;336:1365-1372
Full Text | Web of Science | Medline2
Zeng W ,Maciejewski JP ,Chen G ,Young NS . Limited heterogeneity of T-cell receptor VB usage in aplastic anemia. J Clin Invest 2001;108:765-773
CrossRef | Web of Science | Medline3
Risitano AM ,Maciejewski JP ,Green S ,Plasilova M ,Zeng W ,Young NS . In-vivo dominant immune responses in aplastic anaemia: molecular tracking of putatively pathogenetic T-cell clones by TCR beta-CDR3 sequencing. Lancet 2004;364:355-364
CrossRef | Web of Science | Medline4
Young NS . Acquired aplastic anemia. Ann Intern Med 2002;136:534-546
Web of Science | Medline5
Alter BP. Inherited bone marrow failure syndromes: introduction. In: Young NS, Alter BP, eds. Aplastic anemia, acquired and inherited. Philadelphia: W.B. Saunders, 1994:271-4.
6
Heiss NS ,Knight SW ,Vulliamy TJ , et al. X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions. Nat Genet 1998;19:32-38
CrossRef | Web of Science | Medline7
Knight SW ,Heiss NS ,Vulliamy TJ , et al. X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene. Am J Hum Genet 1999;65:50-58
CrossRef | Web of Science | Medline8
Mitchell JR ,Wood E ,Collins K . A telomerase component is defective in the human disease dyskeratosis congenita. Nature 1999;402:551-555
CrossRef | Web of Science | Medline9
Vulliamy T ,Marrone A ,Goldman F , et al. The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature 2001;413:432-435
CrossRef | Web of Science | Medline10
Theimer CA ,Finger LD ,Trantirek L ,Feigon J . Mutations linked to dyskeratosis congenita cause changes in the structural equilibrium in telomerase RNA. Proc Natl Acad Sci U S A 2003;100:449-454
CrossRef | Web of Science | Medline11
Ruggero D ,Grisendi S ,Piazza F , et al. Dyskeratosis congenita and cancer in mice deficient in ribosomal RNA modification. Science 2003;299:259-262
CrossRef | Web of Science | Medline12
Vulliamy T ,Marrone A ,Szydlo R ,Walne A ,Mason PJ ,Dokal I . Disease anticipation is associated with progressive telomere shortening in families with dyskeratosis congenita due to mutations in TERC. Nat Genet 2004;36:447-449
CrossRef | Web of Science | Medline13
Olovnikov AM . A theory of marginotomy: the incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. J Theor Biol 1973;41:181-190
CrossRef | Web of Science | Medline14
Cong YS ,Wright WE ,Shay JW . Human telomerase and its regulation. Microbiol Mol Biol Rev 2002;66:407-425
CrossRef | Web of Science | Medline15
Stewart SA ,Weinberg RA . Telomerase and human tumorigenesis. Semin Cancer Biol 2000;10:399-406
CrossRef | Web of Science | Medline16
Harrington L . Biochemical aspects of telomerase function. Cancer Lett 2003;194:139-154
CrossRef | Web of Science | Medline17
Pogacic V ,Dragon F ,Filipowicz W . Human H/ACA small nucleolar RNPs and telomerase share evolutionarily conserved proteins NHP2 and NOP10. Mol Cell Biol 2000;20:9028-9040
CrossRef | Web of Science | Medline18
Collins K ,Mitchell JR . Telomerase in the human organism. Oncogene 2002;21:564-579
CrossRef | Web of Science | Medline19
Lingner J ,Hughes TR ,Shevchenko A ,Mann M ,Lundblad V ,Cech TR . Reverse transcriptase motifs in the catalytic subunit of telomerase. Science 1997;276:561-567
CrossRef | Web of Science | Medline20
Ball SE ,Gibson FM ,Rizzo S ,Tooze JA ,Marsh JCW ,Gordon-Smith EC . Progressive telomere shortening in aplastic anemia. Blood 1998;91:3582-3592
Web of Science | Medline21
Brummendorf TH ,Maciejewski JP ,Mak J ,Young NS ,Lansdorp PL . Telomere length in leukocyte subpopulations of patients with aplastic anemia. Blood 2001;97:895-900
CrossRef | Web of Science | Medline22
Vulliamy T ,Marrone A ,Dokal I ,Mason PJ . Association between aplastic anaemia and mutations in telomerase RNA. Lancet 2002;359:2168-2170
CrossRef | Web of Science | Medline23
Calado RT ,Pintao MC ,Silva WA Jr ,Falcao RP ,Zago MA . Aplastic anaemia and telomerase RNA mutations. Lancet 2002;360:1608-1608
CrossRef | Web of Science | Medline24
Fogarty PF ,Yamaguchi H ,Wiestner A , et al. Late presentation of dyskeratosis congenita as apparently acquired aplastic anaemia due to mutations in telomerase RNA. Lancet 2003;362:1628-1630
CrossRef | Web of Science | Medline25
Yamaguchi H ,Baerlocher GM ,Lansdorp PL , et al. Mutations of the human telomerase RNA gene (TERC) in aplastic anemia and myelodysplastic syndrome. Blood 2003;102:916-918
CrossRef | Web of Science | Medline26
Kaufman DW, Kelly JP, Levy M, Shapiro S. The drug etiology of agranulocytosis and aplastic anemia. New York: Oxford University Press, 1991.
27
Packer BR ,Yeager M ,Staats B , et al. SNP500Cancer: a public resource for sequence validation and assay development for genetic variation in candidate genes. Nucleic Acids Res 2004;32:D528-D532
CrossRef | Web of Science | Medline28
Baerlocher GM ,Lansdorp PL . Telomere length measurements in leukocyte subsets by automated multicolor flow-FISH. Cytometry 2003;55:1-6
CrossRef | Medline29
Ly H ,Blackburn EH ,Parslow TG . Comprehensive structure-function analysis of the core domain of human telomerase RNA. Mol Cell Biol 2003;23:6849-6856
CrossRef | Web of Science | Medline30
Blackburn EH . Switching and signaling at the telomere. Cell 2001;106:661-673
CrossRef | Web of Science | Medline31
Moriarty TJ ,Huard S ,Dupuis S ,Autexier C . Functional multimerization of human telomerase requires an RNA interaction domain in the N terminus of the catalytic subunit. Mol Cell Biol 2002;22:1253-1265
CrossRef | Web of Science | Medline32
Moriarty TJ ,Marie-Egyptienne DT ,Autexier C . Functional organization of repeat addition processivity and DNA synthesis determinants in the human telomerase multimer. Mol Cell Biol 2004;24:3720-3733
CrossRef | Web of Science | Medline33
Ly H ,Xu L ,Rivera MA ,Parslow TG ,Blackburn EH . A role for a novel `trans-pseudoknot' RNA-RNA interaction in the functional dimerization of human telomerase. Genes Dev 2003;17:1078-1083
CrossRef | Web of Science | Medline34
Wenz C ,Enenkel B ,Amacker M ,Kelleher C ,Damm K ,Lingner J . Human telomerase contains two cooperating telomerase RNA molecules. EMBO J 2001;20:3526-3534
CrossRef | Web of Science | Medline35
Beattie TL ,Zhou W ,Robinson MO ,Harrington L . Functional multimerization of the human telomerase reverse transcriptase. Mol Cell Biol 2001;21:6151-6160
CrossRef | Web of Science | Medline36
Arai K ,Masutomi K ,Khurts S ,Kaneko S ,Kobayashi K ,Murakami S . Two independent regions of human telomerase reverse transcriptase are important for its oligomerization and telomerase activity. J Biol Chem 2002;277:8538-8544
CrossRef | Web of Science | Medline37
Nakamura TM ,Morin GB ,Chapman KB , et al. Telomerase catalytic subunit homologs from fission yeast and human. Science 1997;277:955-959
CrossRef | Web of Science | Medline38
Armbruster BN ,Banik SSR ,Guo C ,Smith AC ,Counter CM . N-terminal domains of the human telomerase catalytic subunit required for enzyme activity in vivo. Mol Cell Biol 2001;21:7775-7786
CrossRef | Web of Science | Medline39
Banik SSR ,Guo C ,Smith AC , et al. C-terminal regions of the human telomerase catalytic subunit essential for in vivo enzyme activity. Mol Cell Biol 2002;22:6234-6246
CrossRef | Web of Science | Medline40
Bryan TM ,Goodrich KJ ,Cech TR . Telomerase RNA bound by protein motifs specific to telomerase reverse transcriptase. Mol Cell 2000;6:493-499
CrossRef | Web of Science | Medline41
Ly H ,Calado RT ,Allard P , et al. Functional characterization of telomerase RNA variants found in patients with hematologic disorders. Blood 2005;105:2332-2339
CrossRef | Web of Science | Medline42
Marrone A ,Stevens D ,Vulliamy T ,Dokal I ,Mason PJ . Heterozygous telomerase RNA mutations found in dyskeratosis congenita and aplastic anemia reduce telomerase activity via haploinsufficiency. Blood 2004;104:3936-3942
CrossRef | Web of Science | Medline43
Liu Y ,Snow BE ,Hande MP , et al. The telomerase reverse transcriptase is limiting and necessary for telomerase function in vivo. Curr Biol 2000;10:1459-1462[Erratum, Curr Biol 2001;11:907.]
CrossRef | Web of Science | Medline44
Zhang A ,Zheng C ,Hou M , et al. Deletion of the telomerase reverse transcriptase gene and haploinsufficiency of telomere maintenance in Cri du chat syndrome. Am J Hum Genet 2003;72:940-948
CrossRef | Web of Science | Medline45
Kiss AM ,Jady BE ,Bertrand E ,Kiss T . Human box H/ACA pseudouridylation guide RNA machinery. Mol Cell Biol 2004;24:5797-5807
CrossRef | Web of Science | Medline46
Lee HW ,Blasco MA ,Gottlieb GJ ,Horner JW II ,Greider CW ,DePinho RA . Essential role of mouse telomerase in highly proliferative organs. Nature 1998;392:569-574
CrossRef | Web of Science | Medline47
Blasco MA ,Lee HW ,Hande MP , et al. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 1997;91:25-34
CrossRef | Web of Science | Medline48
Rudolph KL ,Chang S ,Lee HW , et al. Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 1999;96:701-712
CrossRef | Web of Science | Medline49
Maciejewski JP ,Follmann D ,Nakamura R , et al. Increased frequency of HLA-DR2 in patients with paroxysmal nocturnal hemoglobinuria and the PNH/aplastic anemia syndrome. Blood 2001;98:3513-3519
CrossRef | Web of Science | Medline50
Saunthararajah Y ,Nakamura R ,Nam JM , et al. HLA-DR15 (DR2) is overrepresented in myelodysplastic syndrome and aplastic anemia and predicts a response to immunosuppression in myelodysplastic syndrome. Blood 2002;100:1570-1574
Web of Science | Medline51
Dufour C ,Capasso M ,Svahn J , et al. Homozygosis for (12) CA repeats in the first intron of the human IFN-gamma gene is significantly associated with the risk of aplastic anemia in Caucasian population. Br J Haematol 2004;126:682-685
CrossRef | Web of Science | Medline52
Peng J ,Liu C ,Zhu K , et al. The TNF2 allele is a risk factor to severe aplastic anemia independent of HLA-DR. Hum Immunol 2003;64:896-901
CrossRef | Web of Science | Medline
- Citing Articles (167)
Citing Articles
1
Ceri H. Jones, Chris Pepper, Duncan M. Baird. (2012) Telomere dysfunction and its role in haematological cancer. British Journal of Haematologyno-no
CrossRef2
Hugo Y K Lam, Michael J Clark, Rui Chen, Rong Chen, Georges Natsoulis, Maeve O'Huallachain, Frederick E Dewey, Lukas Habegger, Euan A Ashley, Mark B Gerstein, Atul J Butte, Hanlee P Ji, Michael Snyder. (2011) Performance comparison of whole-genome sequencing platforms. Nature Biotechnology 30:1, 78-82
CrossRef3
Torbjørn Elvsåshagen, Elsa Vera, Erlend Bøen, Jorunn Bratlie, Ole A. Andreassen, Dag Josefsen, Ulrik F. Malt, Maria A. Blasco, Birgitte Boye. (2011) The load of short telomeres is increased and associated with lifetime number of depressive episodes in bipolar II disorder. Journal of Affective Disorders 135:1-3, 43-50
CrossRef4
Philip J. Mason, Monica Bessler. (2011) The genetics of dyskeratosis congenita. Cancer Genetics 204:12, 635-645
CrossRef5
I. Dokal. (2011) Dyskeratosis Congenita. Hematology 2011:1, 480-486
CrossRef6
C. M. Niemeyer, I. Baumann. (2011) Classification of Childhood Aplastic Anemia and Myelodysplastic Syndrome. Hematology 2011:1, 84-89
CrossRef7
P. G. Surtees, N. W. J. Wainwright, K. A. Pooley, R. N. Luben, K.-T. Khaw, D. F. Easton, A. M. Dunning. (2011) Life Stress, Emotional Health, and Mean Telomere Length in the European Prospective Investigation into Cancer (EPIC)-Norfolk Population Study. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 66A:11, 1152-1162
CrossRef8
Joshua D. Podlevsky, Julian J.-L. Chen. (2011) It all comes together at the ends: Telomerase structure, function, and biogenesis. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
CrossRef9
Mary Armanios. (2011) Telomerase and idiopathic pulmonary fibrosis. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
CrossRef10
R T Calado, J N Cooper, H M Padilla-Nash, E M Sloand, C O Wu, P Scheinberg, T Ried, N S Young. (2011) Short telomeres result in chromosomal instability in hematopoietic cells and precede malignant evolution in human aplastic anemia. Leukemia
CrossRef11
S. Sekulovic, V. Gylfadottir, I. Vulto, M. Gasparetto, Y. Even, C. Brookes, C. Smith, C. J. Eaves, P. M. Lansdorp, F. M. Rossi, R. K. Humphries. (2011) Prolonged self-renewal activity unmasks telomerase control of telomere homeostasis and function of mouse hematopoietic stem cells. Blood 118:7, 1766-1773
CrossRef12
Marta Gladych, Aneta Wojtyla, Blazej Rubis. (2011) Human telomerase expression regulation. Biochemistry and Cell Biology 89:4, 359-376
CrossRef13
Wolfgang Füreder, Peter Valent. (2011) Treatment of refractory or relapsed acquired aplastic anemia: review of established and experimental approaches. Leukemia & Lymphoma 52:8, 1435-1445
CrossRef14
Dana E Rollison, P. K Epling-Burnette, Jong Y Park, Ji-Hyun Lee, Hyun Park, Kristen Jonathan, Ashley L Cole, Jeffrey S Painter, Mayenha Guerrier, Johana MelÉndez-Santiago, William Fulp, Rami Komrokji, Jeffrey Lancet, Alan F List. (2011) Telomere length in myelodysplastic syndromes. Leukemia & Lymphoma 52:8, 1528-1536
CrossRef15
Bruno Bernardes de Jesus, Kerstin Schneeberger, Elsa Vera, Agueda Tejera, Calvin B. Harley, Maria A. Blasco. (2011) The telomerase activator TA-65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence. Aging Cell 10:4, 604-621
CrossRef16
Charles C. Chung, Stephen J. Chanock. (2011) Current status of genome-wide association studies in cancer. Human Genetics 130:1, 59-78
CrossRef17
Jichun Chen. (2011) Hematopoietic stem cell development, aging and functional failure. International Journal of Hematology 94:1, 3-10
CrossRef18
Lijian Shao, Hongliang Li, Senthil K. Pazhanisamy, Aimin Meng, Yong Wang, Daohong Zhou. (2011) Reactive oxygen species and hematopoietic stem cell senescence. International Journal of Hematology 94:1, 24-32
CrossRef19
Nya D. Nelson, Alison A. Bertuch. (2011) Dyskeratosis congenita as a disorder of telomere maintenance. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
CrossRef20
Seiji Kojima, Shinji Nakao, Neal Young, Andrea Bacigalupo, Gerard Gerard, Naoto Hirano, Jaroslaw Maciejewski, Joachim Deeg, Judith Marsh, Feng-Kui Zhang, Jong Wook Lee, Keiya Ozawa. (2011) The Third Consensus Conference on the treatment of aplastic anemia. International Journal of Hematology 93:6, 832-837
CrossRef21
E. M. Parry, J. K. Alder, X. Qi, J. J.- L. Chen, M. Armanios. (2011) Syndrome complex of bone marrow failure and pulmonary fibrosis predicts germline defects in telomerase. Blood 117:21, 5607-5611
CrossRef22
Rodrigo T. Calado, Jennifer Brudno, Paulomi Mehta, Joseph J. Kovacs, Colin Wu, Marco A. Zago, Stephen J. Chanock, Thomas D. Boyer, Neal S. Young. (2011) Constitutional telomerase mutations are genetic risk factors for cirrhosis. Hepatology 53:5, 1600-1607
CrossRef23
Daniel Hartmann, Ujala Srivastava, Michaela Thaler, Karin N. Kleinhans, Gisèle N'Kontchou, Annika Scheffold, Kerstin Bauer, Ramona F. Kratzer, Natalia Kloos, Sarah-Fee Katz, Zhangfa Song, Yvonne Begus-Nahrmann, Alexander Kleger, Guido von Figura, Pavel Strnad, André Lechel, Cagatay Günes, Andrej Potthoff, Katja Deterding, Heiner Wedemeyer, Zhenyu Ju, Ge Song, Feng Xiao, Sonja Gillen, Hubert Schrezenmeier, Thomas Mertens, Marianne Ziol, Helmut Friess, Michael Jarek, Michael P. Manns, Michel Beaugrand, K. Lenhard Rudolph. (2011) Telomerase gene mutations are associated with cirrhosis formation. Hepatology 53:5, 1608-1617
CrossRef24
Erin M. Buckingham, Aloysius J. Klingelhutz. (2011) The role of telomeres in the ageing of human skin. Experimental Dermatology 20:4, 297-302
CrossRef25
Paula Martínez, María A. Blasco. (2011) Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins. Nature Reviews Cancer 11:3, 161-176
CrossRef26
Adam J. Linley, Murrium Ahmad, Robert C. Rees. (2011) Tumour-associated antigens: considerations for their use in tumour immunotherapy. International Journal of Hematology 93:3, 263-273
CrossRef27
Toyoki Maeda, J. -I. Oyama, M. Sasaki, T. Arima, N. Makino. (2011) The correlation between the clinical laboratory data and the telomere length in peripheral blood leukocytes of Japanese female patients with hypertension. The journal of nutrition, health & aging 15:3, 240-244
CrossRef28
Dah-Ching Ding, Tang-Yuan Chu, Shih-Hwa Chiou, Hwan-Wun Liu. (2011) Enhanced differentiation and clonogenicity of human endometrial polyp stem cells. Differentiation 81:3, 172-180
CrossRef29
Jillian E. Koziel, Melanie J. Fox, Catherine E. Steding, Alyssa A. Sprouse, Brittney-Shea Herbert. (2011) Medical genetics and epigenetics of telomerase. Journal of Cellular and Molecular Medicine 15:3, 457-467
CrossRef30
I. Colmegna, C. M. Weyand. (2011) Haematopoietic stem and progenitor cells in rheumatoid arthritis. Rheumatology 50:2, 252-260
CrossRef31
Antonio Paolo Beltrami, Daniela Cesselli, Carlo Alberto Beltrami. (2011) At the stem of youth and health. Pharmacology & Therapeutics 129:1, 3-20
CrossRef32
Yahui Kong, Hang Cui, Charusheila Ramkumar, Hong Zhang. (2011) Regulation of Senescence in Cancer and Aging. Journal of Aging Research 2011, 1-15
CrossRef33
Yan Xu. (2011) Chemistry in human telomere biology: structure, function and targeting of telomere DNA/RNA. Chemical Society Reviews 40:5, 2719
CrossRef34
Mark M. Pomerantz, Matthew L. Freedman. (2011) The Genetics of Cancer Risk. The Cancer Journal 17:6, 416-422
CrossRef35
Sharon A. Savage, Alison A. Bertuch. (2010) The genetics and clinical manifestations of telomere biology disorders. Genetics in Medicine 12:12, 753-764
CrossRef36
N. S. Young. (2010) Telomere Biology and Telomere Diseases: Implications for Practice and Research. Hematology 2010:1, 30-35
CrossRef37
Nils Hartmann, Marina Boehner, Franziska Groenen, Roland Kalb. (2010) Telomere length of patients with major depression is shortened but independent from therapy and severity of the disease. Depression and Anxiety 27:12, 1111-1116
CrossRef38
Erik Schoenmakers, Maura Agostini, Catherine Mitchell, Nadia Schoenmakers, Laura Papp, Odelia Rajanayagam, Raja Padidela, Lourdes Ceron-Gutierrez, Rainer Doffinger, Claudia Prevosto, Jian’an Luan, Sergio Montano, Jun Lu, Mireille Castanet, Nick Clemons, Matthijs Groeneveld, Perrine Castets, Mahsa Karbaschi, Sri Aitken, Adrian Dixon, Jane Williams, Irene Campi, Margaret Blount, Hannah Burton, Francesco Muntoni, Dominic O’Donovan, Andrew Dean, Anne Warren, Charlotte Brierley, David Baguley, Pascale Guicheney, Rebecca Fitzgerald, Alasdair Coles, Hill Gaston, Pamela Todd, Arne Holmgren, Kum Kum Khanna, Marcus Cooke, Robert Semple, David Halsall, Nicholas Wareham, John Schwabe, Lucia Grasso, Paolo Beck-Peccoz, Arthur Ogunko, Mehul Dattani, Mark Gurnell, Krishna Chatterjee. (2010) Mutations in the selenocysteine insertion sequence–binding protein 2 gene lead to a multisystem selenoprotein deficiency disorder in humans. Journal of Clinical Investigation 120:12, 4220-4235
CrossRef39
Judith CW Marsh, Neal S Young. 2010. Acquired Aplastic Anaemia. , 206-225.
CrossRef40
Inderjeet S Dokal. 2010. Inherited Aplastic Anaemia/Bone Marrow Failure Syndromes. , 186-205.
CrossRef41
Nobuhiro Nishio, Seiji Kojima. (2010) Recent progress in dyskeratosis congenita. International Journal of Hematology 92:3, 419-424
CrossRef42
Paula Martínez, Maria A. Blasco. (2010) Role of shelterin in cancer and aging. Aging Cell 9:5, 653-666
CrossRef43
H. D. M. Wyatt, S. C. West, T. L. Beattie. (2010) InTERTpreting telomerase structure and function. Nucleic Acids Research 38:17, 5609-5622
CrossRef44
Lisa Mirabello, Kai Yu, Peter Kraft, Immaculata De Vivo, David J. Hunter, Jennifer Prescott, Jason Y.Y. Wong, Nilanjan Chatterjee, Richard B. Hayes, Sharon A. Savage. (2010) The association of telomere length and genetic variation in telomere biology genesa. Human Mutation 31:9, 1050-1058
CrossRef45
Monica Bessler, David B. Wilson, Philip J. Mason. (2010) Dyskeratosis congenita. FEBS Letters 584:17, 3831-3838
CrossRef46
Paula Martinez, Maria Thanasoula, Ana R. Carlos, Gonzalo Gómez-López, Agueda M. Tejera, Stefan Schoeftner, Orlando Dominguez, David G. Pisano, Madalena Tarsounas, Maria A. Blasco. (2010) Mammalian Rap1 controls telomere function and gene expression through binding to telomeric and extratelomeric sites. Nature Cell Biology 12:8, 768-780
CrossRef47
Jian Ping Li, Cui Ling Zheng, Zhong Chao Han. (2010) Abnormal immunity and stem/progenitor cells in acquired aplastic anemia. Critical Reviews in Oncology/Hematology 75:2, 79-93
CrossRef48
Rosa Ana Risques, Konstantin G. Arbeev, Anatoli I. Yashin, Svetlana V. Ukraintseva, George M. Martin, Peter S. Rabinovitch, Junko Oshima. (2010) Leukocyte Telomere Length Is Associated with Disability in Older U.S. Population. Journal of the American Geriatrics Society 58:7, 1289-1298
CrossRef49
Y. J. Chiang, R. T. Calado, K. S. Hathcock, P. M. Lansdorp, N. S. Young, R. J. Hodes. (2010) Telomere length is inherited with resetting of the telomere set-point. Proceedings of the National Academy of Sciences 107:22, 10148-10153
CrossRef50
D. Levy, S. L. Neuhausen, S. C. Hunt, M. Kimura, S.-J. Hwang, W. Chen, J. C. Bis, A. L. Fitzpatrick, E. Smith, A. D. Johnson, J. P. Gardner, S. R. Srinivasan, N. Schork, J. I. Rotter, U. Herbig, B. M. Psaty, M. Sastrasinh, S. S. Murray, R. S. Vasan, M. A. Province, N. L. Glazer, X. Lu, X. Cao, R. Kronmal, M. Mangino, N. Soranzo, T. D. Spector, G. S. Berenson, A. Aviv. (2010) Genome-wide association identifies OBFC1 as a locus involved in human leukocyte telomere biology. Proceedings of the National Academy of Sciences 107:20, 9293-9298
CrossRef51
Michelle F Maritz, Christine E Napier, Victoria W Wen, Karen L MacKenzie. (2010) Targeting telomerase in hematologic malignancy. Future Oncology 6:5, 769-789
CrossRef52
Akiko Shimamura, Blanche P. Alter. (2010) Pathophysiology and management of inherited bone marrow failure syndromes. Blood Reviews 24:3, 101-122
CrossRef53
Duncan M. Baird. (2010) Variation at the TERT locus and predisposition for cancer. Expert Reviews in Molecular Medicine 12,
CrossRef54
A. Narla, B. L. Ebert. (2010) Ribosomopathies: human disorders of ribosome dysfunction. Blood 115:16, 3196-3205
CrossRef55
M. Xie, J. D. Podlevsky, X. Qi, C. J. Bley, J. J. L. Chen. (2010) A novel motif in telomerase reverse transcriptase regulates telomere repeat addition rate and processivity. Nucleic Acids Research 38:6, 1982-1996
CrossRef56
Rosa M Marión, Maria A Blasco. (2010) Telomere rejuvenation during nuclear reprogramming. Current Opinion in Genetics & Development 20:2, 190-196
CrossRef57
Ergün Sahin, Ronald A. DePinho. (2010) Linking functional decline of telomeres, mitochondria and stem cells during ageing. Nature 464:7288, 520-528
CrossRef58
A. D. Irvine, J. E. Mellerio. 2010. Genetics and Genodermatoses. , 1-97.
CrossRef59
Biju George, Vikram Mathews, Auro Viswabandya, Kavitha M. Lakshmi, Alok Srivastava, Mammen Chandy. (2010) ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IS SUPERIOR TO IMMUNOSUPPRESSIVE THERAPY IN INDIAN CHILDREN WITH APLASTIC ANEMIA—A SINGLE-CENTER ANALYSIS OF 100 PATIENTS. Pediatric Hematology-Oncology 27:2, 122-131
CrossRef60
Gloria M Petersen, Laufey Amundadottir, Charles S Fuchs, Peter Kraft, Rachael Z Stolzenberg-Solomon, Kevin B Jacobs, Alan A Arslan, H Bas Bueno-de-Mesquita, Steven Gallinger, Myron Gross, Kathy Helzlsouer, Elizabeth A Holly, Eric J Jacobs, Alison P Klein, Andrea LaCroix, Donghui Li, Margaret T Mandelson, Sara H Olson, Harvey A Risch, Wei Zheng, Demetrius Albanes, William R Bamlet, Christine D Berg, Marie-Christine Boutron-Ruault, Julie E Buring, Paige M Bracci, Federico Canzian, Sandra Clipp, Michelle Cotterchio, Mariza de Andrade, Eric J Duell, J Michael Gaziano, Edward L Giovannucci, Michael Goggins, Göran Hallmans, Susan E Hankinson, Manal Hassan, Barbara Howard, David J Hunter, Amy Hutchinson, Mazda Jenab, Rudolf Kaaks, Charles Kooperberg, Vittorio Krogh, Robert C Kurtz, Shannon M Lynch, Robert R McWilliams, Julie B Mendelsohn, Dominique S Michaud, Hemang Parikh, Alpa V Patel, Petra H M Peeters, Aleksandar Rajkovic, Elio Riboli, Laudina Rodriguez, Daniela Seminara, Xiao-Ou Shu, Gilles Thomas, Anne Tjønneland, Geoffrey S Tobias, Dimitrios Trichopoulos, Stephen K Van Den Eeden, Jarmo Virtamo, Jean Wactawski-Wende, Zhaoming Wang, Brian M Wolpin, Herbert Yu, Kai Yu, Anne Zeleniuch-Jacquotte, Joseph F Fraumeni, Robert N Hoover, Patricia Hartge, Stephen J Chanock. (2010) A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nature Genetics 42:3, 224-228
CrossRef61
Yoichiro Kamatani, Koichi Matsuda, Yukinori Okada, Michiaki Kubo, Naoya Hosono, Yataro Daigo, Yusuke Nakamura, Naoyuki Kamatani. (2010) Genome-wide association study of hematological and biochemical traits in a Japanese population. Nature Genetics 42:3, 210-215
CrossRef62
Toyoki Maeda, Naoki Makino. (2010) Correlations between clinical laboratory data and telomere length in the leukocytes of patients with hypertension. Nippon Ronen Igakkai Zasshi. Japanese Journal of Geriatrics 47:6, 573-577
CrossRef63
C. C. Chung, W. C. S. Magalhaes, J. Gonzalez-Bosquet, S. J. Chanock. (2010) Genome-wide association studies in cancer--current and future directions. Carcinogenesis 31:1, 111-120
CrossRef64
Calado, Rodrigo T., Young, Neal S., . (2009) Telomere Diseases. New England Journal of Medicine 361:24, 2353-2365
Full Text65
Michael Kirwan, Tom Vulliamy, Anna Marrone, Amanda J. Walne, Richard Beswick, Peter Hillmen, Richard Kelly, Andrew Stewart, David Bowen, Stefan O. Schonland, Annika Maria Whittle, Anthony McVerry, Maria Gilleece, Inderjeet Dokal. (2009) Defining the pathogenic role of telomerase mutations in myelodysplastic syndrome and acute myeloid leukemia. Human Mutation 30:11, 1567-1573
CrossRef66
Vicky Rowena Breakey, Stephen Meyn, Vicky Ng, Christopher Allen, Inderjeet Dokal, Peter M. Lansdorp, Oussama Abla, Yigal Dror. (2009) Hepatitis-associated Aplastic Anemia Presenting as a Familial Bone Marrow Failure Syndrome. Journal of Pediatric Hematology/Oncology 31:11, 884-887
CrossRef67
Maria Teresa Landi, Nilanjan Chatterjee, Kai Yu, Lynn R. Goldin, Alisa M. Goldstein, Melissa Rotunno, Lisa Mirabello, Kevin Jacobs, William Wheeler, Meredith Yeager, Andrew W. Bergen, Qizhai Li, Dario Consonni, Angela C. Pesatori, Sholom Wacholder, Michael Thun, Ryan Diver, Martin Oken, Jarmo Virtamo, Demetrius Albanes, Zhaoming Wang, Laurie Burdette, Kimberly F. Doheny, Elizabeth W. Pugh, Cathy Laurie, Paul Brennan, Rayjean Hung, Valerie Gaborieau, James D. McKay, Mark Lathrop, John McLaughlin, Ying Wang, Ming-Sound Tsao, Margaret R. Spitz, Yufei Wang, Hans Krokan, Lars Vatten, Frank Skorpen, Egil Arnesen, Simone Benhamou, Christine Bouchard, Andres Metsapalu, Tonu Vooder, Mari Nelis, Kristian Välk, John K. Field, Chu Chen, Gary Goodman, Patrick Sulem, Gudmar Thorleifsson, Thorunn Rafnar, Timothy Eisen, Wiebke Sauter, Albert Rosenberger, Heike Bickeböller, Angela Risch, Jenny Chang-Claude, H. Erich Wichmann, Kari Stefansson, Richard Houlston, Christopher I. Amos, Joseph F. Fraumeni, Sharon A. Savage, Pier Alberto Bertazzi, Margaret A. Tucker, Stephen Chanock, Neil E. Caporaso. (2009) A Genome-wide Association Study of Lung Cancer Identifies a Region of Chromosome 5p15 Associated with Risk for Adenocarcinoma. The American Journal of Human Genetics 85:5, 679-691
CrossRef68
R. T. Calado, J. A. Regal, S. Kajigaya, N. S. Young. (2009) Erosion of telomeric single-stranded overhang in patients with aplastic anaemia carrying telomerase complex mutations. European Journal of Clinical Investigation 39:11, 1025-1032
CrossRef69
R. T. Calado, W. T. Yewdell, K. L. Wilkerson, J. A. Regal, S. Kajigaya, C. A. Stratakis, N. S. Young. (2009) Sex hormones, acting on the TERT gene, increase telomerase activity in human primary hematopoietic cells. Blood 114:11, 2236-2243
CrossRef70
Peter M Lansdorp. (2009) Telomeres and disease. The EMBO Journal 28:17, 2532-2540
CrossRef71
Sharon A. Savage, Inderjeet Dokal, Mary Armanios, Geraldine Aubert, Edward W. Cowen, Demetrio L. Domingo, Neelam Giri, Mark H. Greene, Paul J. Orchard, Jakub Tolar, Ekaterini Tsilou, Carter Van Waes, Judy M.Y. Wong, Neal S. Young, Blanche P. Alter. (2009) Dyskeratosis congenita: The first NIH clinical research workshop. Pediatric Blood & Cancer 53:3, 520-523
CrossRef72
R. GONZALEZ-CASAS, L. GARCIA-BUEY, E. A. JONES, J. P. GISBERT, R. MORENO-OTERO. (2009) Systematic review: hepatitis-associated aplastic anaemia - a syndrome associated with abnormal immunological function. Alimentary Pharmacology & Therapeutics 30:5, 436-443
CrossRef73
Mary Armanios. (2009) Syndromes of Telomere Shortening. Annual Review of Genomics and Human Genetics 10:1, 45-61
CrossRef74
Mark Hills, Peter M. Lansdorp. (2009) Short Telomeres Resulting from Heritable Mutations in the Telomerase Reverse Transcriptase Gene Predispose for a Variety of Malignancies. Annals of the New York Academy of Sciences 1176:1, 178-190
CrossRef75
Stefan Schoeftner, Maria A Blasco. (2009) A ‘higher order’ of telomere regulation: telomere heterochromatin and telomeric RNAs. The EMBO Journal 28:16, 2323-2336
CrossRef76
M. Hills, K. Lucke, E. A. Chavez, C. J. Eaves, P. M. Lansdorp. (2009) Probing the mitotic history and developmental stage of hematopoietic cells using single telomere length analysis (STELA). Blood 113:23, 5765-5775
CrossRef77
Eva C. Guinan. (2009) Acquired Aplastic Anemia in Childhood. Hematology/Oncology Clinics of North America 23:2, 171-191
CrossRef78
Sharon A. Savage, Blanche P. Alter. (2009) Dyskeratosis Congenita. Hematology/Oncology Clinics of North America 23:2, 215-231
CrossRef79
Amanda J. Walne, Inderjeet Dokal. (2009) Advances in the understanding of dyskeratosis congenita. British Journal of Haematology 145:2, 164-172
CrossRef80
Michael Kirwan, Inderjeet Dokal. (2009) Dyskeratosis congenita, stem cells and telomeres. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1792:4, 371-379
CrossRef81
Nicholas D. Allen, Duncan M. Baird. (2009) Telomere length maintenance in stem cell populations. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1792:4, 324-328
CrossRef82
Simona Pigullo, Elisa Pavesi, Irma Dianzani, Giuseppe Santamaria, Johanna Svahn, Marco Risso, Maria Teresa Van Lint, Marta Pillon, A.P. Iori, Daniela Longoni, Ugo Ramenghi, Marina Lanciotti, Carlo Dufour. (2009) NOLA1 gene mutations in acquired aplastic anemia. Pediatric Blood & Cancer 52:3, 376-378
CrossRef83
L Bernard, C Belisle, L Mollica, S Provost, D-C Roy, D G Gilliland, R L Levine, L Busque. (2009) Telomere length is severely and similarly reduced in JAK2V617F-positive and -negative myeloproliferative neoplasms. Leukemia 23:2, 287-291
CrossRef84
Rosa M. Marion, Katerina Strati, Han Li, Agueda Tejera, Stefan Schoeftner, Sagrario Ortega, Manuel Serrano, Maria A. Blasco. (2009) Telomeres Acquire Embryonic Stem Cell Characteristics in Induced Pluripotent Stem Cells. Cell Stem Cell 4:2, 141-154
CrossRef85
R. T. Calado, J. A. Regal, M. Hills, W. T. Yewdell, L. F. Dalmazzo, M. A. Zago, P. M. Lansdorp, D. Hogge, S. J. Chanock, E. H. Estey, R. P. Falcao, N. S. Young. (2009) Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia. Proceedings of the National Academy of Sciences 106:4, 1187-1192
CrossRef86
R. T. Calado. (2009) Telomeres and marrow failure. Hematology 2009:1, 338-343
CrossRef87
Jessica A. Box, Jeremy T. Bunch, Wen Tang, Peter Baumann. (2008) Spliceosomal cleavage generates the 3′ end of telomerase RNA. Nature 456:7224, 910-914
CrossRef88
Alexander Röth, Dirk de Beer, Holger Nückel, Ludger Sellmann, Ulrich Dührsen, Jan Dürig, Gabriela M. Baerlocher. (2008) Significantly shorter telomeres in T-cells of patients with ZAP-70 + /CD38 + chronic lymphocytic leukaemia. British Journal of Haematology 143:3, 383-386
CrossRef89
Sharyn Bayne, Margaret EE Jones, He Li, Alex R Pinto, Evan R Simpson, Jun-Ping Liu. (2008) Estrogen deficiency leads to telomerase inhibition, telomere shortening and reduced cell proliferation in the adrenal gland of mice. Cell Research 18:11, 1141-1150
CrossRef90
Antonia Tomás-Loba, Ignacio Flores, Pablo J. Fernández-Marcos, María L. Cayuela, Antonio Maraver, Agueda Tejera, Consuelo Borrás, Ander Matheu, Peter Klatt, Juana M. Flores, José Viña, Manuel Serrano, Maria A. Blasco. (2008) Telomerase Reverse Transcriptase Delays Aging in Cancer-Resistant Mice. Cell 135:4, 609-622
CrossRef91
A. J. Walne, T. Vulliamy, R. Beswick, M. Kirwan, I. Dokal. (2008) TINF2 mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosis congenita and related bone marrow failure syndromes. Blood 112:9, 3594-3600
CrossRef92
H.-Y. Du, E. Pumbo, J. Ivanovich, P. An, R. T. Maziarz, U. M. Reiss, D. Chirnomas, A. Shimamura, A. Vlachos, J. M. Lipton, R. K. Goyal, F. Goldman, D. B. Wilson, P. J. Mason, M. Bessler. (2008) TERC and TERT gene mutations in patients with bone marrow failure and the significance of telomere length measurements. Blood 113:2, 309-316
CrossRef93
Roi Gazit, Irving L. Weissman, Derrick J. Rossi. (2008) Hematopoietic Stem Cells and the Aging Hematopoietic System. Seminars in Hematology 45:4, 218-224
CrossRef94
J. K. Alder, J. J.-L. Chen, L. Lancaster, S. Danoff, S.-c. Su, J. D. Cogan, I. Vulto, M. Xie, X. Qi, R. M. Tuder, J. A. Phillips, P. M. Lansdorp, J. E. Loyd, M. Y. Armanios. (2008) Short telomeres are a risk factor for idiopathic pulmonary fibrosis. Proceedings of the National Academy of Sciences 105:35, 13051-13056
CrossRef95
Neal S Young, Phillip Scheinberg, Rodrigo T Calado. (2008) Aplastic anemia. Current Opinion in Internal Medicine 7:4, 338-344
CrossRef96
Leslie A. Fecher. 2008. Overview of Molecular Pathways inMelanoma. , 9-26.
CrossRef97
B.-W. Gu, M. Bessler, P. J. Mason. (2008) A pathogenic dyskerin mutation impairs proliferation and activates a DNA damage response independent of telomere length in mice. Proceedings of the National Academy of Sciences 105:29, 10173-10178
CrossRef98
Yusheng Cong, Jerry W Shay. (2008) Actions of human telomerase beyond telomeres. Cell Research 18:7, 725-732
CrossRef99
T. Vulliamy, R. Beswick, M. Kirwan, A. Marrone, M. Digweed, A. Walne, I. Dokal. (2008) From the Cover: Mutations in the telomerase component NHP2 cause the premature ageing syndrome dyskeratosis congenita. Proceedings of the National Academy of Sciences 105:23, 8073-8078
CrossRef100
Inderjeet Dokal, Tom Vulliamy. (2008) Inherited aplastic anaemias/bone marrow failure syndromes. Blood Reviews 22:3, 141-153
CrossRef101
R. T. Calado, N. S. Young. (2008) Telomere maintenance and human bone marrow failure. Blood 111:9, 4446-4455
CrossRef102
Neal S Young, Phillip Scheinberg, Rodrigo T Calado. (2008) Aplastic anemia. Current Opinion in Hematology 15:3, 162-168
CrossRef103
Karthik A. Ganapathi, Akiko Shimamura. (2008) Ribosomal dysfunction and inherited marrow failure. British Journal of Haematology 141:3, 376-387
CrossRef104
Junko Takeuchi, Hinh Ly, Hiroki Yamaguchi, Kathryn A. Carroll, Fumiko Kosaka, Kazuhiro Sawaguchi, Yoshio Mitamura, Ayako Watanabe, Seiji Gomi, Koiti Inokuchi, Kazuo Dan. (2008) Identification and functional characterization of novel telomerase variant alleles in Japanese patients with bone-marrow failure syndromes. Blood Cells, Molecules, and Diseases 40:2, 185-191
CrossRef105
Michael Kirwan, Tom Vulliamy, Richard Beswick, Amanda J. Walne, Colin Casimir, Inderjeet Dokal. (2008) Circulating haematopoietic progenitors are differentially reduced amongst subtypes of dyskeratosis congenita. British Journal of Haematology 140:6, 719-722
CrossRef106
James A. McCaul, Katrina E. Gordon, Fay Minty, Janis Fleming, E. Kenneth Parkinson. (2008) Telomere dysfunction is related to the intrinsic radio-resistance of human oral cancer cells. Oral Oncology 44:3, 261-269
CrossRef107
P. M. Lansdorp. (2008) Telomeres, stem cells, and hematology. Blood 111:4, 1759-1766
CrossRef108
Sharon A. Savage, Neelam Giri, Gabriela M. Baerlocher, Nick Orr, Peter M. Lansdorp, Blanche P. Alter. (2008) TINF2, a Component of the Shelterin Telomere Protection Complex, Is Mutated in Dyskeratosis Congenita. The American Journal of Human Genetics 82:2, 501-509
CrossRef109
M Kirwan, I Dokal. (2008) Dyskeratosis congenita: a genetic disorder of many faces. Clinical Genetics 73:2, 103-112
CrossRef110
Derrick J. Rossi, Catriona H.M. Jamieson, Irving L. Weissman. (2008) Stems Cells and the Pathways to Aging and Cancer. Cell 132:4, 681-696
CrossRef111
T.J. Vulliamy, I. Dokal. (2008) Dyskeratosis congenita: The diverse clinical presentation of mutations in the telomerase complex. Biochimie 90:1, 122-130
CrossRef112
Stefan Zimmermann, Uwe M. Martens. (2008) Telomeres, senescence, and hematopoietic stem cells. Cell and Tissue Research 331:1, 79-90
CrossRef113
Zhenyu Ju, Lenhard Rudolph. (2008) Telomere dysfunction and stem cell ageing. Biochimie 90:1, 24-32
CrossRef114
Robert H. Vonderheide. (2008) Prospects and challenges of building a cancer vaccine targeting telomerase. Biochimie 90:1, 173-180
CrossRef115
J. D. Podlevsky, C. J. Bley, R. V. Omana, X. Qi, J. J.-L. Chen. (2007) The Telomerase Database. Nucleic Acids Research 36:Database, D339-D343
CrossRef116
A. Marrone, A. Walne, H. Tamary, Y. Masunari, M. Kirwan, R. Beswick, T. Vulliamy, I. Dokal. (2007) Telomerase reverse-transcriptase homozygous mutations in autosomal recessive dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome. Blood 110:13, 4198-4205
CrossRef117
A Röth, J Dürig, H Himmelreich, S Bug, R Siebert, U Dührsen, P M Lansdorp, G M Baerlocher. (2007) Short telomeres and high telomerase activity in T-cell prolymphocytic leukemia. Leukemia 21:12, 2456-2462
CrossRef118
H.-Y. Du, E. Pumbo, P. Manley, J. J. Field, S. J. Bayliss, D. B. Wilson, P. J. Mason, M. Bessler. (2007) Complex inheritance pattern of dyskeratosis congenita in two families with 2 different mutations in the telomerase reverse transcriptase gene. Blood 111:3, 1128-1130
CrossRef119
Maria A Blasco. (2007) Telomere length, stem cells and aging. Nature Chemical Biology 3:10, 640-649
CrossRef120
Hong-Yan Du, Rachel Idol, Sara Robledo, Jennifer Ivanovich, Ping An, Arturo Londono-Vallejo, David B. Wilson, Philip J. Mason, Monica Bessler. (2007) Telomerase reverse transcriptase haploinsufficiency and telomere length in individuals with 5p- syndrome. Aging Cell 6:5, 689-697
CrossRef121
Norman E. Sharpless, Ronald A. DePinho. (2007) How stem cells age and why this makes us grow old. Nature Reviews Molecular Cell Biology 8:9, 703-713
CrossRef122
Josu De La Fuente, Inderjeet Dokal. (2007) Dyskeratosis congenita: Advances in the understanding of the telomerase defect and the role of stem cell transplantation. Pediatric Transplantation 11:6, 584-594
CrossRef123
B. P. Alter, G. M. Baerlocher, S. A. Savage, S. J. Chanock, B. B. Weksler, J. P. Willner, J. A. Peters, N. Giri, P. M. Lansdorp. (2007) Very short telomere length by flow fluorescence in situ hybridization identifies patients with dyskeratosis congenita. Blood 110:5, 1439-1447
CrossRef124
Toren Finkel, Manuel Serrano, Maria A. Blasco. (2007) The common biology of cancer and ageing. Nature 448:7155, 767-774
CrossRef125
R. T. Calado, S. A. Graf, K. L. Wilkerson, S. Kajigaya, P. J. Ancliff, Y. Dror, S. J. Chanock, P. M. Lansdorp, N. S. Young. (2007) Mutations in the SBDS gene in acquired aplastic anemia. Blood 110:4, 1141-1146
CrossRef126
R Tiu, L Gondek, C O'Keefe, J P Maciejewski. (2007) Clonality of the stem cell compartment during evolution of myelodysplastic syndromes and other bone marrow failure syndromes. Leukemia 21:8, 1648-1657
CrossRef127
Martin Stern, Andreas S. Buser, Andreas Lohri, André Tichelli, Catherine Nissen-Druey. (2007) Autoimmunity and malignancy in hematology—More than an association. Critical Reviews in Oncology/Hematology 63:2, 100-110
CrossRef128
Mark W. Drummond, Stefan Balabanov, Tessa L. Holyoake, Tim H. Brummendorf. (2007) Concise Review: Telomere Biology in Normal and Leukemic Hematopoietic Stem Cells. Stem Cells 25:8, 1853-1861
CrossRef129
Erik R. Westin, Elizabeth Chavez, Kimberly M. Lee, Francoise A. Gourronc, Soraya Riley, Peter M. Lansdorp, Frederick D. Goldman, Aloysius J. Klingelhutz. (2007) Telomere restoration and extension of proliferative lifespan in dyskeratosis congenita fibroblasts. Aging Cell 6:3, 383-394
CrossRef130
Carl H. June. (2007) Principles of adoptive T cell cancer therapy. Journal of Clinical Investigation 117:5, 1204-1212
CrossRef131
K. D. Tsakiri, J. T. Cronkhite, P. J. Kuan, C. Xing, G. Raghu, J. C. Weissler, R. L. Rosenblatt, J. W. Shay, C. K. Garcia. (2007) Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proceedings of the National Academy of Sciences 104:18, 7552-7557
CrossRef132
Armanios, Mary Y., Chen, Julian J.-L., Cogan, Joy D., Alder, Jonathan K., Ingersoll, Roxann G., Markin, Cheryl, Lawson, William E., Xie, Mingyi, Vulto, Irma, Phillips, John A. III, Lansdorp, Peter M., Greider, Carol W., Loyd, James E., . (2007) Telomerase Mutations in Families with Idiopathic Pulmonary Fibrosis. New England Journal of Medicine 356:13, 1317-1326
Full Text133
Gabriela M. Baerlocher, Karen Rice, Irma Vulto, Peter M. Lansdorp. (2007) Longitudinal data on telomere length in leukocytes from newborn baboons support a marked drop in stem cell turnover around 1
year of age. Aging Cell 6:1, 121-123
CrossRef134
Jeffrey K. Davies, Eva C. Guinan. (2007) An update on the management of severe idiopathic aplastic anaemia in children. British Journal of Haematology 136:4, 549-564
CrossRef135
Hiroki Yamaguchi. (2007) Mutations of Telomerase Complex Genes Linked to Bone Marrow Failures. Journal of Nippon Medical School 74:3, 202-209
CrossRef136
JW Shay, WE Wright. (2007) Hallmarks of telomeres in ageing research. The Journal of Pathology 211:2, 114-123
CrossRef137
Jessica F Bell, Norman E Sharpless. (2007) Telomeres, p21 and the cancer-aging hypothesis. Nature Genetics 39:1, 11-12
CrossRef138
Helen B. Fleisig, Judy M.Y. Wong. (2007) Telomerase as a clinical target: Current strategies and potential applications. Experimental Gerontology 42:1-2, 102-112
CrossRef139
Gabriela M Baerlocher, Irma Vulto, Gary de Jong, Peter M Lansdorp. (2006) Flow cytometry and FISH to measure the average length of telomeres (flow FISH). Nature Protocols 1:5, 2365-2376
CrossRef140
Peter M. Lansdorp. (2006) Stress, social rank and leukocyte telomere length. Aging Cell 5:6, 583-584
CrossRef141
Nele Hug, Joachim Lingner. (2006) Telomere length homeostasis. Chromosoma 115:6, 413-425
CrossRef142
Yaroslava G. Yingling, Bruce A. Shapiro. (2006) The prediction of the wild-type telomerase RNA pseudoknot structure and the pivotal role of the bulge in its formation. Journal of Molecular Graphics and Modelling 25:2, 261-274
CrossRef143
Theresa Zucchero, Shawn Ahmed. (2006) Genetics of proliferative aging. Experimental Gerontology 41:10, 992-1000
CrossRef144
Elizabeth H Blackburn, Carol W Greider, Jack W Szostak. (2006) Telomeres and telomerase: the path from maize, Tetrahymena and yeast to human cancer and aging. Nature Medicine 12:10, 1133-1138
CrossRef145
T H Brümmendorf, S Balabanov. (2006) Telomere length dynamics in normal hematopoiesis and in disease states characterized by increased stem cell turnover. Leukemia 20:10, 1706-1716
CrossRef146
Sharon A. Savage, Brian J. Stewart, Babette B. Weksler, Gabriela M. Baerlocher, Peter M. Lansdorp, Stephen J. Chanock, Blanche P. Alter. (2006) Mutations in the reverse transcriptase component of telomerase (TERT) in patients with bone marrow failure. Blood Cells, Molecules, and Diseases 37:2, 134-136
CrossRef147
Tom Vulliamy, Inderjeet Dokal. (2006) Dyskeratosis Congenita. Seminars in Hematology 43:3, 157-166
CrossRef148
Gollob, Michael H., Jones, Douglas L., Krahn, Andrew D., Danis, Lynne, Gong, Xiang-Qun, Shao, Qing, Liu, Xiaoqin, Veinot, John P., Tang, Anthony S.L., Stewart, Alexandre F.R., Tesson, Frederique, Klein, George J., Yee, Raymond, Skanes, Allan C., Guiraudon, Gerard M., Ebihara, Lisa, Bai, Donglin, . (2006) Somatic Mutations in the Connexin 40 Gene (GJA5) in Atrial Fibrillation. New England Journal of Medicine 354:25, 2677-2688
Full Text149
Carla A Theimer, Juli Feigon. (2006) Structure and function of telomerase RNA. Current Opinion in Structural Biology 16:3, 307-318
CrossRef150
Anna Marrone, Inderjeet Dokal. (2006) Dyskeratosis congenita: a disorder of telomerase deficiency and its relationship to other diseases. Expert Review of Dermatology 1:3, 463-479
CrossRef151
Kathleen F. Benson, Marshall Horwitz. (2006) Familial leukemia. Best Practice & Research Clinical Haematology 19:2, 269-279
CrossRef152
Sharon A. Savage, Rodrigo T. Calado, Zhong-Tao Xin, Hinh Ly, Neal S. Young, Stephen J. Chanock. (2006) Genetic variation in telomeric repeat binding factors 1 and 2 in aplastic anemia. Experimental Hematology 34:5, 664-671
CrossRef153
T ANDREW, A AVIV, M FALCHI, G SURDULESCU, J GARDNER, X LU, M KIMURA, B KATO, A VALDES, T SPECTOR. (2006) Mapping Genetic Loci That Determine Leukocyte Telomere Length in a Large Sample of Unselected Female Sibling Pairs. The American Journal of Human Genetics 78:3, 480-486
CrossRef154
Rodrigo T. Calado, Jichun Chen. (2006) Telomerase: not just for the elongation of telomeres. BioEssays 28:2, 109-112
CrossRef155
SHINJI NAKAO. (2006) Disease state and treatment of aplastic anemia. Nihon Naika Gakkai Zasshi 95:9, 1851-1857
CrossRef156
Ling-Yang Hao, Mary Armanios, Margaret A. Strong, Baktiar Karim, David M. Feldser, David Huso, Carol W. Greider. (2005) Short Telomeres, even in the Presence of Telomerase, Limit Tissue Renewal Capacity. Cell 123:6, 1121-1131
CrossRef157
Jichun Chen. (2005) Senescence of Hematopoietic Stem Cells and Bone Marrow Failure. International Journal of Hematology 82:3, 190-195
CrossRef158
Sharon A. Savage, Brian J. Stewart, Andrew Eckert, Maureen Kiley, Jason S. Liao, Stephen J. Chanock. (2005) Genetic variation, nucleotide diversity, and linkage disequilibrium in seven telomere stability genes suggest that these genes may be under constraint. Human Mutation 26:4, 343-350
CrossRef159
Amanda J. Walne, Anna Marrone, Inderjeet Dokal. (2005) Dyskeratosis Congenita: A Disorder of Defective Telomere Maintenance?. International Journal of Hematology 82:3, 184-189
CrossRef160
Sergey S. Akimov, Ali Ramezani, Teresa S. Hawley, Robert G. Hawley. (2005) Bypass of Senescence, Immortalization, and Transformation of Human Hematopoietic Progenitor Cells. Stem Cells 23:9, 1423-1433
CrossRef161
Sharyn Bayne, Jun-Ping Liu. (2005) Hormones and growth factors regulate telomerase activity in ageing and cancer. Molecular and Cellular Endocrinology 240:1-2, 11-22
CrossRef162
Maria A. Blasco. (2005) Telomeres and human disease: ageing, cancer and beyond. Nature Reviews Genetics 6:8, 611-622
CrossRef163
Peter M. Lansdorp. (2005) Major cutbacks at chromosome ends. Trends in Biochemical Sciences 30:7, 388-395
CrossRef164
Lea Harrington. (2005) Making the most of a little: dosage effects in eukaryotic telomere length maintenance. Chromosome Research 13:5, 493-504
CrossRef165
PETER M. LANSDORP. (2005) Role of Telomerase in Hematopoietic Stem Cells. Annals of the New York Academy of Sciences 1044:1, 220-227
CrossRef166
Fibbe, Willem E., . (2005) Telomerase Mutations in Aplastic Anemia. New England Journal of Medicine 352:14, 1481-1483
Full Text167
M. ARMANIOS, C.W. GREIDER. (2005) Telomerase and Cancer Stem Cells. Cold Spring Harbor Symposia on Quantitative Biology 70:1, 205-208
CrossRef
