ArticleLeukemia2012
C-terminal mutation of RUNX1 attenuates the DNA-damage repair response in hematopoietic stem cells.
Article in Leukemia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.
What it found
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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
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- The Role of TP53 Gene Codon 72 Polymorphism in Leukemia: A PRISMA-Compliant Systematic Review and Meta-Analysis.Medicine · 2015Pooled it
- Correlations between MDM2 gene SNP309 polymorphism and susceptibility to leukemia.Medical science monitor : international medical journal of experimental and clinical research · 2015Pooled it
- Impact of RUNX1 mutations at distinct sites on the clinical characteristics and prognosis of patients with acute myeloid leukemia.BMC cancer · 2026Article
- The splicing factor PTBP1 interacts with RUNX1 and is required for leukemia cell survival.Leukemia · 2026Article
- The Dual Role of RUNX1 in Inflammation-Driven Age-Related Diseases: From Molecular Mechanisms to Clinical Translation.Biomedicines · 2025Review
- RUNX1 C-terminal mutations impair blood cell differentiation by perturbing specific enhancer-promoter networks.Blood advances · 2024Article
- Runx1-R188Q germ line mutation induces inflammation and predisposition to hematologic malignancies in mice.Blood advances · 2023Article
- RUNX1 mutations mitigate quiescence to promote transformation of hematopoietic progenitors in Fanconi anemia.Leukemia · 2023Article
- Review
- Review
- Gadd45 in Normal Hematopoiesis and Leukemia.Advances in experimental medicine and biology · 2022Article
- [RUNX1 gene mutations are associated with adverse prognosis of patients with acute myeloidleukemia].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2020Article
- Article
- Role of RUNX Family Transcription Factors in DNA Damage Response.Molecules and cells · 2020Review
- RUNX1-ETO: Attacking the Epigenome for Genomic Instable Leukemia.International journal of molecular sciences · 2019Review
- Review
- Helicase-like transcription factor is a RUNX1 target whose downregulation promotes genomic instability and correlates with complex cytogenetic features in acute myeloid leukemia.Haematologica · 2016Article
- Level of RUNX1 activity is critical for leukemic predisposition but not for thrombocytopenia.Blood · 2015Article
- Article
- The RUNX family: developmental regulators in cancer.Nature reviews. Cancer · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Loss-of-function mutations of RUNX1 have been found in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDSs). Although several reports have suggested roles for RUNX1 as a tumor suppressor, its precise function remains unknown. Because gene alterations of RUNX1 by themselves do not lead to the development of leukemia in mouse models, additional mutation(s) would be required for leukemia development. Here, we report that the C-terminal deletion mutant of RUNX1, RUNX1dC, attenuates DNA-damage repair responses in hematopoietic stem/progenitor cells. γH2AX foci, which indicate the presence of DNA double-strand breaks, were more abundantly accumulated in RUNX1dC-transduced lineage(-)Sca1(+)c-kit(+) (LSK) cells than in mock-transduced LSK cells both in a steady state and after γ-ray treatment. Expression profiling by real-time -PCR array revealed RUNX1dC represses the expression of Gadd45a, a sensor of DNA stress. Furthermore, bone marrow cells from MDS/AML patients harboring the RUNX1-C-terminal mutation showed significantly lower levels of GADD45A expression compared with those from MDS/AML patients with wild-type RUNX1. As for this mechanism, we found that RUNX1 directly regulates the transcription of GADD45A and that RUNX1 and p53 synergistically activate the GADD45A transcription. Together, these results suggest Gadd45a dysfunction due to RUNX1 mutations can cause additional mutation(s) required for multi-step leukemogenesis.
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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.