ArticleProceedings of the National Academy of Sciences of the United States of America2009
Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
111 citing papers in PubMed, 1 synthesis or guideline pooled it, 184 citations in OpenAlex.
- Telomerase reverse transcriptase locus polymorphisms and cancer risk: a field synopsis and meta-analysis.Journal of the National Cancer Institute · 2012Pooled it
- Trial
- Telomere Length Recovery: A Strong Predictor of Overall Survival in Acute Promyelocytic Leukemia.Acta haematologica · 2016Trial
- Trial
- Established and emerging non-cellular therapies in inherited bone marrow failure syndromes.Frontiers in immunology · 2026Review
- Telomerase activity in T-cells as a functional test for pathogenicity assessment of novel genetic variants in telomere biology disorders.Scientific reports · 2025Article
- Autophagy: The convergence point of aging and cancer.Biochemistry and biophysics reports · 2025Review
- Hematological complications in solid organ transplant recipients with telomere biology disorders: a narrative review.Frontiers in immunology · 2025Review
- Genetics of female and male reproductive traits and their relationship with health, longevity and consequences for offspring.Nature aging · 2024Review
- Intraoperative rapid molecular diagnosis aids glioma subtyping and guides precise surgical resection.Annals of clinical and translational neurology · 2024Article
- Clinical mutations in the TERT and TERC genes coding for telomerase components induced oxidative stress, DNA damage at telomeres and cell apoptosis besides decreased telomerase activity.Human molecular genetics · 2024Article
- Predicted leukocyte telomere length and risk of myeloid neoplasms.Human molecular genetics · 2023Article
- Inherited Chromosomally Integrated Human Herpesvirus 6: Laboratory and Clinical Features.Microorganisms · 2023Article
- Telomere dysfunction in some pediatric congenital and growth-related diseases.Frontiers in pediatrics · 2023Review
- Biomarkers of Bladder Cancer: Cell-Free DNA, Epigenetic Modifications and Non-Coding RNAs.International journal of molecular sciences · 2022Review
- Article
- Article
- Imetelstat Induces Leukemia Stem Cell Death in Pediatric Acute Myeloid Leukemia Patient-Derived Xenografts.Journal of clinical medicine · 2022Article
- Lung Fibroblasts from Idiopathic Pulmonary Fibrosis Patients Harbor Short and Unstable Telomeres Leading to Chromosomal Instability.Biomedicines · 2022Article
- A whole-exome case-control association study to characterize the contribution of rare coding variation to pancreatic cancer risk.HGG advances · 2022Article
51 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
Loss-of-function mutations in telomerase complex genes can cause bone marrow failure, dyskeratosis congenita, and acquired aplastic anemia, both diseases that predispose to acute myeloid leukemia. Loss of telomerase function produces short telomeres, potentially resulting in chromosome recombination, end-to-end fusion, and recognition as damaged DNA. We investigated whether mutations in telomerase genes also occur in acute myeloid leukemia. We screened bone marrow samples from 133 consecutive patients with acute myeloid leukemia and 198 controls for variations in TERT and TERC genes. An additional 89 patients from a second cohort, selected based on cytogenetic status, and 528 controls were further examined for mutations. A third cohort of 372 patients and 384 controls were specifically tested for one TERT gene variant. In the first cohort, 11 patients carried missense TERT gene variants that were not present in controls (P < 0.0001); in the second cohort, TERT mutations were associated with trisomy 8 and inversion 16. Mutation germ-line origin was demonstrated in 5 patients from whom other tissues were available. Analysis of all 3 cohorts (n = 594) for the most common gene variant (A1062T) indicated a prevalence 3 times higher in patients than in controls (n = 1,110; P = 0.0009). Introduction of TERT mutants into telomerase-deficient cells resulted in loss of enzymatic activity by haploinsufficiency. Inherited mutations in TERT that reduce telomerase activity are risk factors for acute myeloid leukemia. We propose that short and dysfunctional telomeres limit normal stem cell proliferation and predispose for leukemia by selection of stem cells with defective DNA damage responses that are prone to genome instability.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.