ArticleThe Journal of experimental medicine2015
Cohesin loss alters adult hematopoietic stem cell homeostasis, leading to myeloproliferative neoplasms.
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Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.
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125citing papers in PubMed
8.1field-weighted citation impact, top 2% of its field
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Who cites it
125 citing papers in PubMed, 161 citations in OpenAlex.
- Article
- The effect of cohesin mutations on HLA-class II expression in the myeloid leukemia of Down syndrome.Leukemia · 2026Article
- Targeting SMC3 deacetylation synergizes with XPO1 inhibition to reprogram the epigenetic landscape and suppress NPM1-mutated acute myeloid leukemia.Nature communications · 2026Article
- Rapid reduction in global chromatin loop size after acute STAG2 reconstitution in human cancer cells.bioRxiv : the preprint server for biology · 2026Article
- Tumour necrosis factor receptor-associated factor 7 drives leukaemogenesis through the TWIST1-P2RX1-CaJournal of translational medicine · 2026Article
- Successful treatment of relapsed FLT3-mutated donor cell-derived MDS/AML with FLT3 inhibitor gilteritinib.Annals of hematology · 2026Article
- Epigenetic Regulation of Higher-Order Chromatin Structure (HOCS) and Its Implication in Human Diseases.Cancers · 2026Review
- Cohesin haploinsufficiency is tolerated in Cbfb::MYH11-driven murine acute myeloid leukemia.Experimental hematology · 2026Article
- A Novel Therapeutic Strategy for Bone Marrow Failure: Niche Rejuvenation Using Costal Cartilage-Derived Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- STAG2 regulates polycomb and differentiation in urothelial precursors and bladder cancer.PloS one · 2025Article
- The Functions and Mechanisms of the Cohesin Complex in Regulating the Fate Determinations of Stem Cells.Research (Washington, D.C.) · 2025Review
- Untangling the loops ofLeukemia & lymphoma · 2025Review
- Cohesin mutations in acute myeloid leukemia.Leukemia · 2024Review
- CohesinLife (Basel, Switzerland) · 2024Article
- Subunit-specific analysis of cohesin-mutant myeloid malignancies reveals distinct ontogeny and outcomes.Leukemia · 2024Article
- Yin Yang 1 regulates cohesin complex protein SMC3 in mouse hematopoietic stem cells.Blood advances · 2024Article
- Chromatin organization in myelodysplastic syndrome.Experimental hematology · 2024Review
- Malignant progression of preleukemic disorders.Blood · 2024Review
- Role of chromosomal cohesion and separation in aneuploidy and tumorigenesis.Cellular and molecular life sciences : CMLS · 2024Review
- Splicing modulators impair DNA damage response and induce killing of cohesin-mutant MDS and AML.Science translational medicine · 2024Article
65 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 3 institutions in 1 country.
Jasper MullendersHoward Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016 Howard Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016.
Beatriz Aranda-OrgillesHoward Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016 Howard Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016.
Priscillia LhoumaudHoward Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016.
Matthew KellerHoward Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016 Howard Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016.
Juhee PaeHoward Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016 Howard Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016.
Kun WangHoward Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016 Howard Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016.
Clarisse KayembeHoward Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016 Howard Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016.
Pedro P RochaHoward Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016.
Ramya RaviramHoward Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016.
Yixiao GongHoward Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016 Howard Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016.
Prem K PremsrirutMirimus Inc., Woodbury, NY 11797.
Aristotelis TsirigosHoward Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016 Howard Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016.
Richard BonneauHoward Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016.
Jane A SkokHoward Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016.
Luisa CimminoHoward Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016 Howard Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016.
Daniela HoehnDepartment of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032.
Iannis AifantisHoward Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016 Howard Hughes Medical Institute, Department of Pathology, and Center for Health Informatics and Bioinformatics, School of Medicine and Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY 10016 Iannis.Aifantis@nyumc.org.
New York University · USHoward Hughes Medical Institute · USColumbia University Irving Medical Center · US
Funding
Project-005UL1TR001445 · NCATS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BREDELLA, MIRIAM ANTOINETTE, HOCHMAN, JUDITH S · 2015 to 2025
$103.5MVaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ADRIANA HEGUY · 1985 to 2026
$83.1MInstitutional Clinical and Translational Science AwardUL1TR000038 · NCATS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CRONSTEIN, BRUCE NEIL, HOCHMAN, JUDITH S · 2012 to 2014
$16.8MRole of TET2 mutations in malignant transformation and acute myeloid leukemiaR01CA173636 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI AIFANTIS, IANNIS, LEVINE, ROSS L · 2013 to 2022
$6.3MRole Of Nuclear Organization In Protecting Genome Stability During RecombinationR01GM086852 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KLUGER, YUVAL, SKOK, JANE AMANDA · 2008 to 2016
$3.8MThe role of the SCF/FBW7 ubiquitin ligase complex in hematopiesis and leukemia.R01CA133379 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI AIFANTIS, IANNIS · 2009 to 2018
$3.6MRegulation of hematopoietic stem cell differentiationR01CA105129 · NCI · UNIVERSITY OF CHICAGO · PI AIFANTIS, IANNIS · 2005 to 2014
$2.8MLong non-coding RNAs in hematopoiesis and blood malignancyR01CA194923 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI AIFANTIS, IANNIS · 2015 to 2019
$2.3MMechanisms of T cell leukemia induction and maintenanceR01CA149655 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI AIFANTIS, IANNIS · 2010 to 2015
$2.0MGenetic Dissection of Acute Myeloid Leukemia.R01CA169784 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI AIFANTIS, IANNIS, LEVINE, ROSS L · 2014 to 2018
$1.8MEnhancer Driven Gene Regulation During Lymphocyte DevelopmentR01GM112192 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI SKOK, JANE AMANDA · 2014 to 2016
$1.6MHoward Hughes Medical InstituteNCATS NIH HHS UL1 TR000038NCATS NIH HHS UL1 TR00038NCATS NIH HHS UL1 TR001445NCI NIH HHS 1R01CA105129NCI NIH HHS 1R01CA133379NCI NIH HHS 1R01CA149655NCI NIH HHS 1R01CA169784NCI NIH HHS 5R01CA173636NCI NIH HHS 5R01CA194923NCI NIH HHS P30 CA016087NCI NIH HHS P30CA016087NCI NIH HHS R01 CA105129NCI NIH HHS R01 CA133379NCI NIH HHS R01 CA149655NCI NIH HHS R01 CA169784NCI NIH HHS R01 CA173636NCI NIH HHS R01 CA194923NIGMS NIH HHS R01 GM086852NIGMS NIH HHS R01 GM112192
Abstract
The cohesin complex (consisting of Rad21, Smc1a, Smc3, and Stag2 proteins) is critically important for proper sister chromatid separation during mitosis. Mutations in the cohesin complex were recently identified in a variety of human malignancies including acute myeloid leukemia (AML). To address the potential tumor-suppressive function of cohesin in vivo, we generated a series of shRNA mouse models in which endogenous cohesin can be silenced inducibly. Notably, silencing of cohesin complex members did not have a deleterious effect on cell viability. Furthermore, knockdown of cohesin led to gain of replating capacity of mouse hematopoietic progenitor cells. However, cohesin silencing in vivo rapidly altered stem cells homeostasis and myelopoiesis. Likewise, we found widespread changes in chromatin accessibility and expression of genes involved in myelomonocytic maturation and differentiation. Finally, aged cohesin knockdown mice developed a clinical picture closely resembling myeloproliferative disorders/neoplasms (MPNs), including varying degrees of extramedullary hematopoiesis (myeloid metaplasia) and splenomegaly. Our results represent the first successful demonstration of a tumor suppressor function for the cohesin complex, while also confirming that cohesin mutations occur as an early event in leukemogenesis, facilitating the potential development of a myeloid malignancy.
Indexed as
HomeostasisAdultAnimalsCell Cycle ProteinsCell DifferentiationChromatinChromosomal Proteins, Non-HistoneCohesinsHematopoietic Stem CellsHumansMiceMyeloproliferative DisordersTumor Suppressor ProteinsCell Cycle ProteinsChromatinChromosomal Proteins, Non-HistoneCohesinsTumor Suppressor Proteins
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