Association of Telomere Length of Peripheral Blood Leukocytes With Hematopoietic Relapse, Malignant Transformation, and Survival in Severe Aplastic Anemia
Open accessAbstract
CONTEXT: Critically short telomeres produce apoptosis, cell senescence, and chromosomal instability in tissue culture and animal models. Variations in telomere length have been reported in severe aplastic anemia but their clinical significance is unknown. OBJECTIVE: To investigate the relationship between telomere length and clinical outcomes in severe aplastic anemia. DESIGN, SETTING, AND PATIENTS: Single institution analysis of 183 patients with severe aplastic anemia who were treated in sequential prospective protocols at the National Institutes of Health from 2000 to 2008. The pretreatment leukocyte age-adjusted telomere length of patients with severe aplastic anemia consecutively enrolled in immunosuppression protocols with antithymocyte globulin plus cyclosporine for correlation with clinical outcomes were analyzed. MAIN OUTCOME MEASURES: Hematologic response, relapse, clonal evolution, and survival. RESULTS: There was no relationship between hematologic response and telomere length with response rates of 56.5% of 46 patients in the first, 54.3% of 46 in the second, 60% of 45 in the third, and 56.5% of 46 in the fourth quartiles. Multivariate analysis demonstrated that telomere length was associated with relapse, clonal evolution, and mortality. Evaluated as a continuous variable, telomere length inversely correlated with the probability of hematologic relapse (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.03-0.69; P = .01). The probability of clonal evolution was higher in patients in the first quartile (24.5%; 95% CI, 8.7%-37.5%) than in quartiles 2 through 4 (8.4%; 95% CI, 3.2%-13.3%; P = .009), and evolution to monosomy 7 or complex cytogenetics was more common in the first quartile (18.8%; 95% CI, 3.5%-31.6%) [corrected] than in quartiles 2 through 4 (4.5%; 95% CI, 0.5%-8.2%; P = .002) [corrected]. Survival between these 2 groups differed, with 66% (95% CI, 52.9%-82.5%) surviving 6 years in the first quartile compared with 83.8% (95% CI, 77.3%-90.9%) in quartiles 2 through 4 (P = .008). CONCLUSION: In a cohort of patients with severe aplastic anemia receiving immunosuppressive therapy, telomere length was unrelated to response but was associated with risk of relapse, clonal evolution, and overall survival.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Patients with aplastic anaemia and shorter telomeres at diagnosis show more severe disease, poorer response to treatment, increased risk of relapse and MDS, and lower survival.
“Patients with shorter telomeres at diagnosis show a more severe disease, a poorer response to treatments, an increased risk of relapse and development of myelodysplastic syndrome (MDS; see below) and a lower survival rate75,80,81.”
From Telomere dysfunction in ageing and age-related diseases (2022) · cites this paper as [80]
The Results (Response and relapse according to telomere length; Clonal evolution and survival according to telomere length) associate shorter pretreatment telomeres with relapse, clonal evolution and lower survival. They do not establish more severe disease at diagnosis, and explicitly report no correlation between telomere length and response to initial immunosuppressive treatment. The paper reports clonal evolution, including changes associated with myelodysplasia, rather than a separate MDS risk estimate. (LLM, conf=0.91)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Telomere measurement by quantitative PCR
Cawthon, R. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.10.e47 · Cited by 3,492 · see citing works
Telomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA
Blasco, M. A., Lee, H.-W., Hande, M. P., Samper, E., Lansdorp, P. M., DePinho, R. A., & Greider, C. W. (1997) · Cell · doi:10.1016/s0092-8674(01)80006-4 · Cited by 2,108 · see citing works
Counter, C. M., Avilion, A. A., LeFeuvre, C. E., Stewart, N. G., Greider, C. W., Harley, C. B., & Bacchetti, S. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05245.x · Cited by 2,096 · see citing works
Telomere reduction in human colorectal carcinoma and with ageing
Hastie, N. D., Dempster, M., Dunlop, M. G., Thompson, A. M., Green, D. K., & Allshire, R. C. (1990) · Nature · doi:10.1038/346866a0 · Cited by 1,650 · see citing works
Hemann, M. T., Strong, M. A., Hao, L.-Y., & Greider, C. W. (2001) · Cell · doi:10.1016/s0092-8674(01)00504-9 · Cited by 1,219 · see citing works
Current concepts in the pathophysiology and treatment of aplastic anemia
Young, N. S., Calado, R. T., & Scheinberg, P. (2006) · Blood · doi:10.1182/blood-2006-03-010777 · Cited by 888 · see citing works
Self-citationTelomeres and telomerase in cancer
Artandi, S. E., & DePinho, R. A. (2010) · Carcinogenesis · doi:10.1093/carcin/bgp268 · Cited by 823 · see citing works
Calado, R. T., & Young, N. S. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0903373 · Cited by 783 · see citing works
Self-citationBrouilette, S., Moore, J. S., McMahon, A. D., Thompson, J. R., Ford, I., Shepherd, J., Packard, C. J., & Samani, N. J. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60071-3 · Cited by 744 · see citing works
Mutations in <i>TERT,</i> the Gene for Telomerase Reverse Transcriptase, in Aplastic Anemia
Yamaguchi, H., Calado, R. T., Ly, H., Kajigaya, S., Baerlocher, G. M., Chanock, S. J., Lansdorp, P. M., & Young, N. S. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa042980 · Cited by 723 · see citing works
Self-citationCancer in dyskeratosis congenita
Alter, B. P., Giri, N., Savage, S. A., & Rosenberg, P. S. (2009) · Blood · doi:10.1182/blood-2008-12-192880 · Cited by 478 · see citing works
Antithymocyte Globulin and Cyclosporine for Severe Aplastic Anemia
Rosenfeld, S. J., Follmann, D. A., Núñez, O., et al. (2003) · JAMA · doi:10.1001/jama.289.9.1130 · Cited by 398 · see citing works
Calado, R. T., Yewdell, W. T., Wilkerson, K. L., Regal, J. A., Kajigaya, S., Stratakis, C. A., & Young, N. S. (2009) · Blood · doi:10.1182/blood-2008-09-178871 · Cited by 362 · see citing works
Self-citationChromosomal instability in ulcerative colitis is related to telomere shortening
O'Sullivan, J. N., Bronner, M. P., Brentnall, T. A., Finley, J. C., Shen, W.-T., Emerson, S., Emond, M. J., Gollahon, K. A., Moskovitz, A. H., Crispin, D. A., et al. (2002) · Nature Genetics · doi:10.1038/ng989 · Cited by 346 · see citing works
Short Telomeres Limit Tumor Progression In Vivo by Inducing Senescence
Feldser, D. M., & Greider, C. W. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.02.026 · Cited by 314 · see citing works
Progressive Telomere Shortening in Aplastic Anemia
Ball, S. E., Gibson, F. M., Rizzo, S., Tooze, J. A., Marsh, J. C. W., & Gordon‐Smith, E. C. (1998) · Blood · doi:10.1182/blood.v91.10.3582 · Cited by 288 · see citing works
Telomere shortening is an early somatic DNA alteration in human prostate tumorigenesis.
Meeker, A. K., Hicks, J. L., Platz, E. A., March, G. E., Bennett, C., Delannoy, M. J., & Marzo, A. M. D. (2002) · PubMed · Cited by 271 · see citing works
Distinct clinical outcomes for cytogenetic abnormalities evolving from aplastic anemia
Maciejewski, J. P., Risitano, A. M., Sloand, E. M., Núñez, O., & Young, N. S. (2002) · Blood · doi:10.1182/blood.v99.9.3129 · Cited by 249 · see citing works
Self-citationTelomere length in leukocyte subpopulations of patients with aplastic anemia
Brümmendorf, T. H., Maciejewski, J. P., Mak, J., Young, N. S., & Lansdorp, P. M. (2001) · Blood · doi:10.1182/blood.v97.4.895 · Cited by 233 · see citing works
Self-citationTelomere maintenance and human bone marrow failure
Calado, R. T., & Young, N. S. (2008) · Blood · doi:10.1182/blood-2007-08-019729 · Cited by 220 · see citing works
Self-citationPredicting response to immunosuppressive therapy and survival in severe aplastic anaemia
Scheinberg, P., Wu, C. O., Núñez, O., & Young, N. S. (2008) · British Journal of Haematology · doi:10.1111/j.1365-2141.2008.07450.x · Cited by 208 · see citing works
Self-citationEngelhardt, M. M., Drullinsky, P. R., Guillem, J. G., & Moore, M. A. S. (1997) · PubMed · Cited by 189 · see citing works
Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia
Calado, R. T., Regal, J. A., Hills, M., Yewdell, W. T., Dalmazzo, L. F., Zago, M. A., Lansdorp, P. M., Hogge, D., Chanock, S. J., Estey, E. H., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0807057106 · Cited by 184 · see citing works
Self-citationRisques, R. A., Lai, L. A., Brentnall, T. A., Li, L., Feng, Z., Gallaher, J. L., Mandelson, M. T., Potter, J. D., Bronner, M. P., & Rabinovitch, P. S. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.04.008 · Cited by 178 · see citing works
Scheinberg, P., Núñez, O., & Young, N. S. (2006) · British Journal of Haematology · doi:10.1111/j.1365-2141.2006.06098.x · Cited by 171 · see citing works
Self-citationScheinberg, P., Wu, C. O., Nunez, O., et al. (2009) · Haematologica · doi:10.3324/haematol.13829 · Cited by 169 · see citing works
Self-citationScheinberg, P., Núñez, O., Wu, C. O., et al. (2006) · British Journal of Haematology · doi:10.1111/j.1365-2141.2006.06085.x · Cited by 155 · see citing works
Self-citationLeukocyte Telomere Length Predicts Cancer Risk in Barrett's Esophagus
Risques, R. A., Vaughan, T. L., Li, X., Odze, R. D., Blount, P. L., Ayub, K., Gallaher, J. L., Reid, B. J., & Rabinovitch, P. S. (2007) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-07-0624 · Cited by 151 · see citing works
Rossi, D., Bodoni, C. L., Genuardi, E., Monitillo, L., Drandi, D., Cerri, M., Deambrogi, C., Ricca, I., Rocci, A., Ferrero, S., et al. (2009) · Leukemia · doi:10.1038/leu.2008.399 · Cited by 100 · see citing works
Telomere Length in Peripheral Blood Predicts Survival in Clear Cell Renal Cell Carcinoma
Svenson, U., Ljungberg, B., & Roos, G. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-3513 · Cited by 92 · see citing works
Short Telomeres Initiate Telomere Recombination in Primary and Tumor Cells
Morrish, T. A., & Greider, C. W. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000357 · Cited by 70 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [24]Artandi SE DePinho RA Telomeres and telomerase in cancer Carcinogenesis 2010 31 1 9 18 19887512 PMC3003493
Cited by
Sorted by citations
Telomere dysfunction in ageing and age-related diseases
Rossiello, F., Jurk, D., Passos, J. F., & d’Adda di Fagagna, F. (2022) · Nature Cell Biology · doi:10.1038/s41556-022-00842-x · Cited by 754 · see citing works
Guidelines for the diagnosis and management of adult aplastic anaemia
Killick, S. B., Bown, N., Cavenagh, J., Dokal, I., Foukaneli, T., Hill, A., Hillmen, P., Ireland, R., Kulasekararaj, A., Mufti, G., et al. (2016) · British Journal of Haematology · doi:10.1111/bjh.13853 · Cited by 749 · see citing works
Somatic Mutations and Clonal Hematopoiesis in Aplastic Anemia
Yoshizato, T., Dumitriu, B., Hosokawa, K., Makishima, H., Yoshida, K., Townsley, D., Sato-Otsubo, A., Sato, Y., Liu, D., Suzuki, H., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1414799 · Cited by 646 · see citing works
Self-citationDanazol Treatment for Telomere Diseases
Townsley, D. M., Dumitriu, B., Liu, D., Biancotto, A., Weinstein, B., Chen, C., Hardy, N., Mihalek, A. D., Lingala, S., Kim, Y. J., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1515319 · Cited by 415 · see citing works
Self-citationTelomere Dynamics in Mice and Humans
Calado, R. T., & Dumitriu, B. (2013) · Seminars in Hematology · doi:10.1053/j.seminhematol.2013.03.030 · Cited by 214 · see citing works
Self-citationZhao, J., Zhu, Y., Lin, J., Matsuguchi, T., Blackburn, E., Zhang, Y., Cole, S. A., Best, L. G., Lee, E. T., & Howard, B. V. (2014) · Diabetes · doi:10.2337/db13-0744 · Cited by 161 · see citing works
Jones, A. M., Beggs, A. D., Carvajal-Carmona, L., Farrington, S., Tenesa, A., Walker, M., Howarth, K., Ballereau, S., Hodgson, S. V., Zauber, A., et al. (2012) · Gut · doi:10.1136/gut.2011.239772 · Cited by 113 · see citing works
Gadalla, S. M., Wang, T., Haagenson, M., Spellman, S. R., Lee, S. J., Williams, K. M., Wong, J. Y., De Vivo, I., & Savage, S. A. (2015) · JAMA · doi:10.1001/jama.2015.7 · Cited by 95 · see citing works
Sakaguchi, H., Nishio, N., Hama, A., Kawashima, N., Wang, X., Narita, A., Doisaki, S., Xu, Y., Muramatsu, H., Yoshida, N., et al. (2014) · Haematologica · doi:10.3324/haematol.2013.091165 · Cited by 47 · see citing works
The wide-ranging clinical implications of the Short Telomere Syndromes
Barbaro, P. M., Ziegler, D. S., & Reddel, R. R. (2016) · Internal Medicine Journal · doi:10.1111/imj.12868 · Cited by 40 · see citing works
- Authors
- Scheinberg, P., Cooper, J. N., Sloand, E. M., Wu, C. O., Calado, R. T., & Young, N. S.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Scheinberg, Phillip
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2010-09-22
- Volume
- 304
- Issue
- 12
- Pages
- 1358
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC3721502
- OpenAlex
- W1992786956
- Cited by
- 205
- References
- 31
- Citations by year
- 2026: 10 · 2025: 4 · 2024: 9 · 2023: 7 · 2022: 7 · 2021: 10 · 2020: 11 · 2019: 13 · 2018: 21 · 2017: 19 · 2016: 13 · 2015: 17 · 2014: 19 · 2013: 14 · 2012: 13
- FWCI
- 9.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 HL999999)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Keywords
- telomere length, severe aplastic anemia, clonal evolution, malignant transformation, survival, peripheral blood leukocytes, monosomy 7, cytogenetics, antithymocyte globulin, cyclosporine, immunosuppressive therapy, hematologic response, prognostic factors, hematopoietic stem cells
- MeSH terms
- Adult, Anemia, Aplastic, Cell Transformation, Neoplastic, Female, Humans, Immunosuppressive Agents, Leukocytes, Male, Prognosis, Recurrence, Cohort Studies, Survival Analysis, Telomere, Treatment Outcome, Chromosomal Instability
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
