ArticleCell stem cell2018
SIRT1 Activation Disrupts Maintenance of Myelodysplastic Syndrome Stem and Progenitor Cells by Restoring TET2 Function.
Open access · bronzeAbstract read
In one paragraph
Article in Cell stem cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
6.6field-weighted citation impact, top 2% of its field
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
61 citing papers in PubMed, 109 citations in OpenAlex.
- Targeting SIRT6 epigenetically restrains neutrophil hyperplasia and enhances chemotherapeutic efficacy.Acta pharmaceutica Sinica. B · 2026Article
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Clonal Hematopoiesis and Gut Microbiota-Derived TMAO as Candidate Amplifiers of Cardiovascular Inflammation: The CHIDT Hypothesis.Antioxidants (Basel, Switzerland) · 2026Review
- Inhibition of ADSS2-mediated de novo AMP biosynthesis re-sensitizes acute myeloid leukemia to BH3 mimetics.Nature cancer · 2026Article
- Inflammageing and clonal haematopoiesis interplay and their impact on human disease.Nature reviews. Molecular cell biology · 2026Review
- Epigenetic inflammatory memory and periodontal disease: Mechanisms and clinical significance for comorbidities.Journal of periodontology · 2026Review
- Metabolic Plasticity in Embryogenesis Throughout the Lens of NADMethods in molecular biology (Clifton, N.J.) · 2026Review
- Base-resolution DNA methylome of human MDS hematopoietic stem cell reveals TET2-GFI1 epigenetic axis repressing MDS.Immunity & inflammation · 2026Article
- Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025Review
- SIRT1 as a masterful reciprocal regulator of molecular mechanisms and signaling pathways involved in tumor growth and expansion.Clinical and experimental medicine · 2025Review
- Regulation of Stem Cell Function by NADPhysiology (Bethesda, Md.) · 2025Review
- Myelodysplastic Neoplasms (MDS): Pathogenesis and Therapeutic Prospects.Biomolecules · 2025Review
- Epigenetic Therapies in Melanoma-Targeting DNA Methylation and Histone Modification.Biomedicines · 2025Review
- Article
- PARP inhibition leads to synthetic lethality with key splicing-factor mutations in myelodysplastic syndromes.British journal of cancer · 2024Article
- Targeting PRMT9-mediated arginine methylation suppresses cancer stem cell maintenance and elicits cGAS-mediated anticancer immunity.Nature cancer · 2024Article
- Loss of TET2 increases B-1 cell number and IgM production while limiting CDR3 diversity.Frontiers in immunology · 2024Article
- TET (Ten-eleven translocation) family proteins: structure, biological functions and applications.Signal transduction and targeted therapy · 2023Review
- Epigenetic Regulators of DNA Cytosine Modification: Promising Targets for Cancer Therapy.Biomedicines · 2023Review
- A Therapeutically Targetable NOTCH1-SIRT1-KAT7 Axis in T-cell Leukemia.Blood cancer discovery · 2023Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
33 authors at 10 institutions in 4 countries.
Jie SunLaboratory of Cancer Biology, Provincial Key Lab of Biotherapy in Zhejiang, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China; Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
Xin HeDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA; Department of Hematology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
Yinghui ZhuDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
Zonghui DingDepartment of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA.
Haojie DongDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
Yimei FengDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA; Department of Hematology, The Second Affiliated Hospital of Army Medical University, Chongqing 400037, China.
Juan DuThe Integrative Genomics Core, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
Hanying WangLaboratory of Cancer Biology, Provincial Key Lab of Biotherapy in Zhejiang, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China; Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
Xiwei WuThe Integrative Genomics Core, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
Lei ZhangThe Translational Biomarker Discovery Core, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
Xiaochun YuDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
Allen LinDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
Tinisha McDonaldDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
Dandan ZhaoDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
Herman WuDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
Wei-Kai HuaDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
Bin ZhangDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
Lifeng FengLaboratory of Cancer Biology, Provincial Key Lab of Biotherapy in Zhejiang, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
Kaoru TohyamaDepartment of Laboratory Medicine, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
Ravi BhatiaDivision of Hematology and Oncology, Department of Medicine, University of Alabama Birmingham, Birmingham, AL 35233, USA.
Philipp OberdoerfferLaboratory for Receptor Biology and Gene Expression, National Cancer Institute, Bethesda, MD 20892, USA.
Yang Jo ChungCenter for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20889, USA.
Peter D AplanCenter for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20889, USA.
Jacqueline BoultwoodNuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK; Haematology Theme, Oxford Biomedical Research Centre, Oxford OX3 9DU, UK.
Andrea PellagattiNuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK; Haematology Theme, Oxford Biomedical Research Centre, Oxford OX3 9DU, UK.
Samer KhaledDepartment of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope Medical Center, Duarte, CA 91010, USA.
Marcin KortylewskiDepartment of Immuno-Oncology, City of Hope Medical Center, Duarte, CA 91010, USA.
Flavia PichiorriDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
Ya-Huei KuoDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
Nadia CarlessoDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
Guido MarcucciDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
Hongchuan JinLaboratory of Cancer Biology, Provincial Key Lab of Biotherapy in Zhejiang, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China. Electronic address: jinhc@zju.edu.cn.
Ling LiDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA. Electronic address: lingli@coh.org.
City of Hope · USBeckman Research InstituteNational Cancer Institute · USCity Of Hope National Medical Center · USOxford BioMedica (United Kingdom) · GBSir Run Run Shaw Hospital · CNKawasaki Medical School · JPMayo Clinic in Arizona · USUniversity of Alabama at Birmingham · USZhejiang University · CN
Funding
XRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Robert S Welner · 1985 to 2026
$165.9MTransgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3MVirology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KITCHEN, SCOTT G · 1991 to 2018
$39.9MRegulation of Ionizing Radiation-Induced DNA Damage ResponseR01CA130899 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LIU, YILUN · 2009 to 2023
$5.5MInvestigating the role of DNA breaks in mammalian agingZIABC011283 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI OBERDOERFFER, PHILIPP · 2010 to 2019
$4.3MTargeting protein acetylation as a therapeutic approach for MDSR01HL141336 · NHLBI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI LI, LING · 2018 to 2022
$2.2MInflammation as determinant of clonal selection in MPN progressionR01HL141379 · NHLBI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI CARLESSO, NADIA · 2018 to 2021
$2.1MPhysiologic Regulation of Hematopoiesis by NotchR01DK097837 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI CARLESSO, NADIA · 2014 to 2017
$1.6MResearch career advancement: Role of the SIRT1 deacetylase in maintenance of FLT3R00CA184411 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI LI, LING · 2015 to 2017
$747kResearch career advancement: Role of the SIRT1 deacetylase in maintenance of FLT3K99CA184411 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI LI, LING · 2014 to 2015
$281kNCI NIH HHS K99 CA184411NCI NIH HHS P30 CA013148NCI NIH HHS P30 CA033572NCI NIH HHS R00 CA184411NCI NIH HHS R01 CA130899NHLBI NIH HHS R01 HL141336NHLBI NIH HHS R01 HL141379NIAID NIH HHS P30 AI028697NIDDK NIH HHS R01 DK097837
Abstract
Myelodysplastic syndrome (MDS), a largely incurable hematological malignancy, is derived from aberrant clonal hematopoietic stem/progenitor cells (HSPCs) that persist after conventional therapies. Defining the mechanisms underlying MDS HSPC maintenance is critical for developing MDS therapy. The deacetylase SIRT1 regulates stem cell proliferation, survival, and self-renewal by deacetylating downstream proteins. Here we show that SIRT1 protein levels were downregulated in MDS HSPCs. Genetic or pharmacological activation of SIRT1 inhibited MDS HSPC functions, whereas SIRT1 deficiency enhanced MDS HSPC self-renewal. Mechanistically, the inhibitory effects of SIRT1 were dependent on TET2, a safeguard against HSPC transformation. SIRT1 deacetylated TET2 at conserved lysine residues in its catalytic domain, enhancing TET2 activity. Our genome-wide analysis identified cancer-related genes regulated by the SIRT1/TET2 axis. SIRT1 activation also inhibited functions of MDS HSPCs from patients with TET2 heterozygous mutations. Altogether, our results indicate that restoring TET2 function through SIRT1 activation represents a promising means to target MDS HSPCs.
Indexed as
AnimalsDioxygenasesDNA-Binding ProteinsHematopoietic Stem CellsHumansMiceMice, Inbred C57BLMice, KnockoutMyelodysplastic SyndromesProto-Oncogene ProteinsSirtuin 1Tumor Cells, CulturedDioxygenasesDNA-Binding ProteinsProto-Oncogene ProteinsSIRT1 protein, humanSirt1 protein, mouseSirtuin 1TET2 protein, humanTet2 protein, mouseacetylationHSPCsmyelodysplastic syndromeSIRT1SRT1720TET2
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
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.