ArticleJCI insight2021
Cohesin mutations alter DNA damage repair and chromatin structure and create therapeutic vulnerabilities in MDS/AML.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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.
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Who cites it
62 citing papers in PubMed, 81 citations in OpenAlex.
- Folding a broken genome: the versatile roles of cohesin in genome maintenance.Nature reviews. Genetics · 2026Review
- Origins and consequences of oncogenic 3D chromatin remodelling.Nature reviews. Cancer · 2026Review
- Context-dependent synthetic lethality - an emerging precision therapeutic approach.Nature reviews. Cancer · 2026Review
- Cohesin mutations and chromatin changes in cancer.International journal of cancer · 2026Review
- Modeling myeloid cell development in health and disease using induced pluripotent stem cells.Frontiers in immunology · 2026Review
- Cohesin haploinsufficiency is tolerated in Cbfb::MYH11-driven murine acute myeloid leukemia.Experimental hematology · 2026Article
- Tumor-suppressive activities of SA1/STAG2 and effects of PARP impairment during brain development.Disease models & mechanisms · 2026Article
- S-phase PARylation of microprotein RSMC enhances the function of Sororin in sister chromatid cohesion.The EMBO journal · 2026Article
- STAG2-truncating variants reveal a mosaic STAG2 inactivation pattern and compensatory mechanisms involving cohesin complex remodeling.iScience · 2025Article
- Splicing Factor Mutations in Chronic Myelomonocytic Leukemia: Biological Consequences and Therapeutic Implications.Current hematologic malignancy reports · 2025Review
- Review
- Epigenetic dysregulation in acute myeloid leukemia.Seminars in hematology · 2025Review
- Myelodysplastic Neoplasms (MDS): Pathogenesis and Therapeutic Prospects.Biomolecules · 2025Review
- STAG2 expression imparts distinct therapeutic vulnerabilities in muscle-invasive bladder cancer cells.Oncogenesis · 2025Article
- Unveiling Myelodysplastic Syndromes: Exploring Pathogenic Mechanisms and Therapeutic Advances.Cancers · 2025Review
- Emerging roles of cohesin-STAG2 in cancer.Oncogene · 2025Review
- Untangling the loops ofLeukemia & lymphoma · 2025Review
- Novel small-molecule therapies for myelodysplastic syndromes with IPSS-R ⩾3.5 in patients aged 60 or older: current landscape and challenges.Therapeutic advances in hematology · 2025Review
- Exploring the role of PARP1 inhibition in enhancing antibody-drug conjugate therapy for acute leukemias: insights from DNA damage response pathway interactions.Journal of translational medicine · 2024Article
- Mapping in silico genetic networks of the KMT2D tumour suppressor gene to uncover novel functional associations and cancer cell vulnerabilities.Genome medicine · 2024Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
23 authors at 6 institutions in 2 countries.
Funding
Abstract
The cohesin complex plays an essential role in chromosome maintenance and transcriptional regulation. Recurrent somatic mutations in the cohesin complex are frequent genetic drivers in cancer, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Here, using genetic dependency screens of stromal antigen 2-mutant (STAG2-mutant) AML, we identified DNA damage repair and replication as genetic dependencies in cohesin-mutant cells. We demonstrated increased levels of DNA damage and sensitivity of cohesin-mutant cells to poly(ADP-ribose) polymerase (PARP) inhibition. We developed a mouse model of MDS in which Stag2 mutations arose as clonal secondary lesions in the background of clonal hematopoiesis driven by tet methylcytosine dioxygenase 2 (Tet2) mutations and demonstrated selective depletion of cohesin-mutant cells with PARP inhibition in vivo. Finally, we demonstrated a shift from STAG2- to STAG1-containing cohesin complexes in cohesin-mutant cells, which was associated with longer DNA loop extrusion, more intermixing of chromatin compartments, and increased interaction with PARP and replication protein A complex. Our findings inform the biology and therapeutic opportunities for cohesin-mutant malignancies.
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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.