ArticleScience translational medicine2023
Phosphorylation stabilized TET1 acts as an oncoprotein and therapeutic target in B cell acute lymphoblastic leukemia.
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Article in Science translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11citing papers in PubMed
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- DNA methylation signatures of sporadic colorectal cancer with microsatellite instability.Epigenetics · 2026Article
- Genomic characterization of resistant and relapsed adult B-cell acute lymphoblastic leukemia.Journal of applied genetics · 2026Article
- TET1 loss propels the development of hyperthyroidism by remodeling histone modifications of PAX8 promoter.Experimental & molecular medicine · 2025Article
- TET1: The epigenetic architect of clinical disease progression.Genes & diseases · 2025Review
- Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025Review
- Screening of pivotal oncogenes modulated by DNA methylation in hepatocellular carcinoma and identification of atractylenolide I as an anti-cancer drug.Human cell · 2025Article
- Article
- CRISPR screening reveals ZNF217 as a vulnerability in high-risk B-cell acute lymphoblastic leukemia.Theranostics · 2025Article
- PPM1G Inhibits Epithelial-Mesenchymal Transition in Cholangiocarcinoma by Catalyzing TET1 Dephosphorylation for Destabilization to Impair Its Targeted Demethylation of the CLDN3 Promoter.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Epigenetic marks or not? The discovery of novel DNA modifications in eukaryotes.The Journal of biological chemistry · 2024Review
- Marine-Derived Bisindoles for Potent Selective Cancer Drug Discovery and Development.Molecules (Basel, Switzerland) · 2024Review
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Authors and funding
40 authors at 10 institutions in 2 countries.
Zhenhua ChenDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.ORCID 0000-0002-1381-0235
Keren ZhouDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.ORCID 0000-0001-7905-3399
Jianhuang XueDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.ORCID 0000-0003-0623-2200
Andrew SmallDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.ORCID 0000-0002-0222-2729
Gang XiaoDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.ORCID 0000-0002-9476-3847
Le Xuan Truong NguyenDepartment of Hematological Malignancies Translational Science, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
Zheng ZhangDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
Emily PrinceDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.ORCID 0000-0002-8972-5248
Hengyou WengDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.ORCID 0000-0001-6474-2861
Huilin HuangDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.ORCID 0000-0003-2608-572X
Zhicong ZhaoDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.ORCID 0000-0002-3225-2494
Ying QingDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.ORCID 0000-0001-6763-6204
Chao ShenDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.ORCID 0000-0002-9406-7075
Wei LiDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
Li HanDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
Brandon TanDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
Rui SuDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.ORCID 0000-0002-4807-6229
Hanjun QinIntegrative Genomics Core, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.ORCID 0000-0002-0370-0913
Yangchan LiDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.ORCID 0000-0002-0354-7621
Dong WuDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
Zhaohui GuDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.ORCID 0000-0003-1581-1327
Vu N NgoDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.ORCID 0000-0002-9501-6990
Xin HeDepartment of Hematological Malignancies Translational Science, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
Jianfei ChaoDivision of Stem Cell Biology Research, Department of Developmental and Stem Cell Biology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.ORCID 0000-0003-4607-9925
Keith LeungDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.ORCID 0000-0003-2662-1625
Kitty WangDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
Lei DongDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.ORCID 0000-0001-9574-0148
Xi QinDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
Zhenming CaiDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.ORCID 0000-0003-0545-5576
Yue ShengDepartment of Medicine and Department of Biochemistry and Molecular Biology, UF Health Cancer Center, University of Florida, Gainesville, FL 32611, USA.ORCID 0000-0002-9424-123X
Yu ChenMolecular Instrumentation Center, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Xiwei WuIntegrative Genomics Core, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.ORCID 0000-0002-7071-1671
Bin ZhangDepartment of Hematological Malignancies Translational Science, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.ORCID 0000-0003-4703-7524
Yanhong ShiDivision of Stem Cell Biology Research, Department of Developmental and Stem Cell Biology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
Guido MarcucciDepartment of Hematological Malignancies Translational Science, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.ORCID 0000-0002-3983-5908
Zhijian QianDepartment of Medicine and Department of Biochemistry and Molecular Biology, UF Health Cancer Center, University of Florida, Gainesville, FL 32611, USA.ORCID 0000-0001-5565-7534
Mingjiang XuDepartment of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.ORCID 0000-0002-7063-6253
Markus MüschenDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
Jianjun ChenDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.ORCID 0000-0003-3749-2902
Xiaolan DengDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.ORCID 0000-0003-3695-0203
City of Hope · USSun Yat-sen University · CNCentral South University · CNGuangzhou Experimental Station · CNShanghai Jiao Tong University · CNThe University of Texas Health Science Center at San Antonio · USTongji University · CNUniversity of California, Los Angeles · USUniversity of Florida Health · USYale Cancer Center · US
Funding
Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI XIWEI WU · 1985 to 2026
$86.3MThe role and therapeutic potential of IGF2BP2 in MLL-rearranged leukemiaR01CA271497 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI Jianjun Chen · 2022 to 2026
$2.8MTargeting FTO to treat acute myeloid leukemiaR01CA243386 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI CHEN, JIANJUN · 2020 to 2024
$2.8MTET2-mediated epitranscriptomic regulation in leukemia microenvironmentR01CA280389 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI Jianjun Chen · 2023 to 2026
$2.7MThe role and mechanism of METTL3/METTL14-mediated RNA modification in the pathogenesis and drug-resistance of AMLR01CA236399 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI CHEN, JIANJUN · 2019 to 2023
$2.3MTargeting TET1 signaling to treat acute myeloid leukemiaR01CA211614 · NCI · UNIVERSITY OF CINCINNATI · PI CHEN, JIANJUN · 2017 to 2021
$2.3MThe function and underlying mechanism of TET1 in myelodysplastic syndromesR01DK124116 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI CHEN, JIANJUN · 2020 to 2023
$2.2MRole of the TET1 short isoform in MDS development and maintenanceR01HL157539 · NHLBI · UNIVERSITY OF FLORIDA · PI QIAN, ZHIJIAN · 2022 to 2025
$2.1MThe role and mechanism of FTO in leukemogenesis and drug responseR01CA214965 · NCI · UNIVERSITY OF CINCINNATI · PI CHEN, JIANJUN · 2017 to 2021
$2.1MDNA Damage Response and Oncogenic SignalingT32CA186895 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI BINGHUI SHEN, Jeremy Michael Stark · 2016 to 2026
$2.1MPotential therapeutic implications of targeting miR-150 in acute myeloid leukemiaR01CA182528 · NCI · UNIVERSITY OF CINCINNATI · PI CHEN, JIANJUN · 2014 to 2018
$1.7MThe role and functional mechanism of TET1 in MLL-rearranged leukemiaR01CA178454 · NCI · UNIVERSITY OF CINCINNATI · PI CHEN, JIANJUN · 2014 to 2018
$1.7MNCI NIH HHS P30 CA033572NCI NIH HHS R01 CA178454NCI NIH HHS R01 CA182528NCI NIH HHS R01 CA211614NCI NIH HHS R01 CA214965NCI NIH HHS R01 CA236399NCI NIH HHS R01 CA243386NCI NIH HHS R01 CA271497NCI NIH HHS R01 CA280389NCI NIH HHS T32 CA186895NHLBI NIH HHS R01 HL157539NIDDK NIH HHS R01 DK124116
Abstract
Although the overall survival rate of B cell acute lymphoblastic leukemia (B-ALL) in childhood is more than 80%, it is merely 30% in refractory/relapsed and adult patients with B-ALL. This demonstrates a need for improved therapy targeting this subgroup of B-ALL. Here, we show that the ten-eleven translocation 1 (TET1) protein, a dioxygenase involved in DNA demethylation, is overexpressed and plays a crucial oncogenic role independent of its catalytic activity in B-ALL. Consistent with its oncogenic role in B-ALL, overexpression of TET1 alone in normal precursor B cells is sufficient to transform the cells and cause B-ALL in mice within 3 to 4 months. We found that TET1 protein is stabilized and overexpressed because of its phosphorylation mediated by protein kinase C epsilon (PRKCE) and ATM serine/threonine kinase (ATM), which are also overexpressed in B-ALL. Mechanistically, TET1 recruits STAT5B to the promoters of
Indexed as
Precursor Cell Lymphoblastic Leukemia-LymphomaProto-Oncogene ProteinsAnimalsDNA-Binding ProteinsMicePhosphorylationSignal TransductionStaurosporineDNA-Binding ProteinsProto-Oncogene ProteinsStaurosporineTET1 protein, mouse
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