ArticleBlood2021
Loss of a 7q gene, CUX1, disrupts epigenetically driven DNA repair and drives therapy-related myeloid neoplasms.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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
15 citing papers in PubMed, 27 citations in OpenAlex.
- T-cell lymphoma of the breast and ovary presenting as a second malignant neoplasm in a pediatric leukemia survivor: A case report and literature review.Rare tumors · 2026Article
- Comprehensive analysis of the potential effect and mechanism of pyroptosis-related genes in treatment-related myeloid tumors.PloS one · 2026Article
- Article
- Ancestry-dependent patterns of somatic mosaicism and clonal hematopoiesis mutations in over 125,000 individuals reveal distinct cancer associations.Human genomics · 2025Article
- NAMPT haploinsufficiency is a collateral lethal therapeutic vulnerability in high-risk myeloid malignancies withBlood neoplasia · 2025Article
- Multiplex gene editing models of del(7q) reveal combinedBlood neoplasia · 2025Article
- Distinct landscape and clinical implications of therapy-related clonal hematopoiesis.The Journal of clinical investigation · 2024Review
- CUX1 attenuates the apoptosis of renal tubular epithelial cells induced by contrast media through activating the PI3K/AKT signaling pathway.BMC nephrology · 2024Article
- CUX1 regulates human hematopoietic stem cell chromatin accessibility via the BAF complex.Cell reports · 2024Article
- Transcriptional Landscape of CUT-Class Homeobox Genes in Blastic Plasmacytoid Dendritic Cell Neoplasm.International journal of molecular sciences · 2024Article
- Germline Variants and Characteristic Features of Hereditary Hematological Malignancy Syndrome.International journal of molecular sciences · 2024Review
- Article
- Outcomes following venetoclax-based treatment in therapy-related myeloid neoplasms.American journal of hematology · 2022Article
- Therapy-related clonal cytopenia as a precursor to therapy-related myeloid neoplasms.Blood cancer journal · 2022Article
- Genomic studies controvert the existence of the CUX1 p75 isoform.Scientific reports · 2022Article
Corrections and comments
- Commented on by
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Therapy-related myeloid neoplasms (t-MNs) are high-risk late effects with poorly understood pathogenesis in cancer survivors. It has been postulated that, in some cases, hematopoietic stem and progenitor cells (HSPCs) harboring mutations are selected for by cytotoxic exposures and transform. Here, we evaluate this model in the context of deficiency of CUX1, a transcription factor encoded on chromosome 7q and deleted in half of t-MN cases. We report that CUX1 has a critical early role in the DNA repair process in HSPCs. Mechanistically, CUX1 recruits the histone methyltransferase EHMT2 to DNA breaks to promote downstream H3K9 and H3K27 methylation, phosphorylated ATM retention, subsequent γH2AX focus formation and propagation, and, ultimately, 53BP1 recruitment. Despite significant unrepaired DNA damage sustained in CUX1-deficient murine HSPCs after cytotoxic exposures, they continue to proliferate and expand, mimicking clonal hematopoiesis in patients postchemotherapy. As a consequence, preexisting CUX1 deficiency predisposes mice to highly penetrant and rapidly fatal therapy-related erythroleukemias. These findings establish the importance of epigenetic regulation of HSPC DNA repair and position CUX1 as a gatekeeper in myeloid transformation.
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.