ArticleMolecular cell2020
Two Aldehyde Clearance Systems Are Essential to Prevent Lethal Formaldehyde Accumulation in Mice and Humans.
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Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed, 2 pooled it
7.8field-weighted citation impact, top 2% of its field
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Who cites it
84 citing papers in PubMed, 2 syntheses or guidelines pooled it, 180 citations in OpenAlex.
- Assessment of associations between inhaled formaldehyde and lymphohematopoietic cancer through the integration of epidemiological and toxicological evidence with biological plausibility.Toxicological sciences : an official journal of the Society of Toxicology · 2024Pooled it
- Genetic architecture of alcohol consumption identified by a genotype-stratified GWAS and impact on esophageal cancer risk in Japanese people.Science advances · 2024Pooled it
- Comparative Analysis of Alcohol and Aldehyde Dehydrogenase Activities in Prostate Cancer and Benign Prostatic Hyperplasia.Journal of clinical medicine · 2026Article
- Excess folate elevates formaldehyde genotoxicity in cell lines but not in mice or humans.EMBO molecular medicine · 2026Article
- Mitochondrial vulnerability to aldehydic load and the role mitochondrial aldehyde dehydrogenases.Pharmacological research · 2026Review
- Aldehyde Detoxification in Cancer: Metabolic Guardians of the Genome.Biomolecules · 2026Review
- Fanconi Anemia as a Window into Premalignant Field Cancerization of the Oral Mucosa.medRxiv : the preprint server for health sciences · 2026Article
- Increased replication-associated single-stranded DNA promotes formaldehyde-induced mutagenesis.bioRxiv : the preprint server for biology · 2026Article
- Metabolic trajectories in developing human neocortical neurons.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Metabolite-induced DNA damage drives stochastic stem cell loss and clonal hematopoiesis.Cell stem cell · 2026Article
- Intranasal Formaldehyde Exposure Induces RAGE-Mediated Alteration of the ADAM10/BACE1 Expression Balance and Amyloid Deposition.Biomedicines · 2026Article
- Mechanisms of transcription-coupled repair and DNA damage surveillance in health and disease.Nature reviews. Molecular cell biology · 2026Review
- Fancl-mutant mice reveal central role of monoubiquitination in Fanconi anemia and a model for therapeutic gene editing.Blood advances · 2026Article
- Tissue-specific mutagenesis from endogenous guanine damage is suppressed by Polκ and DNA repair.Nature communications · 2025Article
- Formate Reduces Ischemic Injury in Female Hearts Lacking Alcohol Dehydrogenase 5.FASEB bioAdvances · 2025Article
- Genotoxic formaldehyde and lipid aldehydes are sources of DNA damage in keratinocytes.bioRxiv : the preprint server for biology · 2025Article
- Occupational exposure to formaldehyde and risk of lymphoma subtypes: results of a multicentre Italian case-control study.Environmental health : a global access science source · 2025Article
- DNA polymerase kappa is the primary translesion synthesis polymerase for aldehyde ICLs.Nucleic acids research · 2025Article
- Translesion polymerases and DNA-protein crosslink repair shapes the cellular response to formaldehyde-induced DNA damage in ssDNA.Nucleic acids research · 2025Article
- G-quadruplexes as a source of vulnerability in BRCA2Proceedings of the National Academy of Sciences of the United States of America · 2025Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
36 authors at 12 institutions in 5 countries.
Felix A DinglerMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Meng WangMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK; Department of Haematology, University of Cambridge, Cambridge, UK.
Anfeng MuLaboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto, Japan; Department of Genome Biology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan; Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
Christopher L MillingtonMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Nina OberbeckMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Sam WatchamDepartment of Haematology, University of Cambridge, Cambridge, UK; Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.
Lucas B PontelMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK; Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA)-CONICET, Polo Científico Tecnológico, Godoy Cruz 2390, C1425FQD Buenos Aires, Argentina.
Ashley N Kamimae-LanningMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Frederic LangevinMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Camille NadlerMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Rebecca L CordellDepartment of Chemistry, University of Leicester, Leicester LE1 7RH, UK.
Paul S MonksDepartment of Chemistry, University of Leicester, Leicester LE1 7RH, UK.
Rui YuDepartment of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.
Nicola K WilsonDepartment of Haematology, University of Cambridge, Cambridge, UK; Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.
Asuka HiraLaboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto, Japan; Department of Genome Biology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
Kenichi YoshidaDepartment of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Minako MoriLaboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto, Japan; Department of Genome Biology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan; Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Yusuke OkamotoLaboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto, Japan; Department of Genome Biology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan; Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Yusuke OkunoDepartment of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Hideki MuramatsuDepartment of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yuichi ShiraishiSection of Genome Analysis Platform, Center for Cancer Genomic and Advanced Therapeutics, National Cancer Center, Tokyo, Japan.
Masayuki KobayashiDepartment of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Hematology, Kyoto Katsura Hospital, Kyoto, Japan.
Toshinori MoriguchiDepartment of Hematology, Kyoto Katsura Hospital, Kyoto, Japan.
Tomoo OsumiChildren's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
Motohiro KatoChildren's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
Satoru MiyanoLaboratory of DNA Information Analysis, Human Genome Center, The Institute of Medical Science, University of Tokyo, Tokyo Japan.
Etsuro ItoDepartment of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Seiji KojimaDepartment of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Hiromasa YabeDepartment of Innovative Medical Science, Tokai University School of Medicine, Isehara, Japan.
Miharu YabeDepartment of Innovative Medical Science, Tokai University School of Medicine, Isehara, Japan.
Keitaro MatsuoDivision of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan; Division of Analytical Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Seishi OgawaDepartment of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institute, Sweden; Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan.
Berthold GöttgensDepartment of Haematology, University of Cambridge, Cambridge, UK; Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.
Michael R G HodskinsonMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Minoru TakataLaboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University, Kyoto, Japan; Department of Genome Biology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan. Electronic address: takata.minoru.8s@kyoto-u.ac.jp.
Ketan J PatelMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK; MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK. Electronic address: kjp@mrc-lmb.cam.ac.uk.
MRC Laboratory of Molecular Biology · GBKyoto University · JPNagoya University · JPWellcome/MRC Cambridge Stem Cell Institute · GBNational Center For Child Health and Development · JPTokai University · JPUniversity of Leicester · GBAichi Cancer Center · JPHirosaki University · JPKyoto Katsura Hospital · JPTokyo University of Science · JPUniversity of North Carolina at Chapel Hill · US
Funding
STOCHASTIC ANALYSIS OF FLOW AND TRANSPORT PHENOMENAP42ES005948 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FRY, REBECCA · 1992 to 2017
$45.4MUNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Stephanie Engel · 2001 to 2026
$36.3MCancer Research UK C60150/A23919Medical Research Council G0902418Medical Research Council MC_PC_12009Medical Research Council MC_PC_15065Medical Research Council MC_PC_17230Medical Research Council MC_U105178811Medical Research Council MC_UU_00016/17Medical Research Council MR/M008975/1NIEHS NIH HHS P30 ES010126NIEHS NIH HHS P42 ES005948Wellcome Trust
Abstract
Reactive aldehydes arise as by-products of metabolism and are normally cleared by multiple families of enzymes. We find that mice lacking two aldehyde detoxifying enzymes, mitochondrial ALDH2 and cytoplasmic ADH5, have greatly shortened lifespans and develop leukemia. Hematopoiesis is disrupted profoundly, with a reduction of hematopoietic stem cells and common lymphoid progenitors causing a severely depleted acquired immune system. We show that formaldehyde is a common substrate of ALDH2 and ADH5 and establish methods to quantify elevated blood formaldehyde and formaldehyde-DNA adducts in tissues. Bone-marrow-derived progenitors actively engage DNA repair but also imprint a formaldehyde-driven mutation signature similar to aging-associated human cancer mutation signatures. Furthermore, we identify analogous genetic defects in children causing a previously uncharacterized inherited bone marrow failure and pre-leukemic syndrome. Endogenous formaldehyde clearance alone is therefore critical for hematopoiesis and in limiting mutagenesis in somatic tissues.
Indexed as
AdolescentAlcohol DehydrogenaseAldehyde Dehydrogenase, MitochondrialAldehydesAnimalsChildChild, PreschoolDNA AdductsDNA DamageDNA RepairFemaleFormaldehydeHematopoiesisHematopoietic Stem CellsHumansInfantAdh5 protein, mouseAlcohol DehydrogenaseAldehyde Dehydrogenase, MitochondrialAldehydesDNA AdductsFormaldehydeageingbone marrow failurecancerDNA damageformaldehydehematopoiesishematopoietic stem cellsimmunodeficiencymutagenesisoncometabolite
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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.