ArticleLeukemia2007
Folate restriction and methylenetetrahydrofolate reductase 677T polymorphism decreases adoMet synthesis via folate-dependent remethylation in human-transformed lymphoblasts.
Article in Leukemia, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Role of methionine metabolism in cancer: recent advances in molecular mechanisms and therapeutic implications.Experimental hematology & oncology · 2026Review
- Development of an Engineered Bacterial Endophyte: Promoting Plant Growth Through Pyrroloquinoline Quinone (PQQ) Synthesis.Microorganisms · 2025Article
- Ketogenic Diet Consumption Inhibited Mitochondrial One-Carbon Metabolism.International journal of molecular sciences · 2022Article
- Article
- MTHFR Knockdown Assists Cell Defense against Folate Depletion Induced Chromosome Segregation and Uracil Misincorporation in DNA.International journal of molecular sciences · 2021Article
- MAT2A Localization and Its Independently Prognostic Relevance in Breast Cancer Patients.International journal of molecular sciences · 2021Article
- Folinate Supplementation Ameliorates Methotrexate Induced Mitochondrial Formate Depletion In Vitro and In Vivo.International journal of molecular sciences · 2021Article
- Transmission Jeopardy of Adenomatosis Polyposis Coli and Methylenetetrahydrofolate Reductase in Colorectal Cancer.Journal of the renin-angiotensin-aldosterone system : JRAAS · 2021Article
- Tracing Metabolic Fate of Mitochondrial Glycine Cleavage System Derived Formate In Vitro and In Vivo.International journal of molecular sciences · 2020Article
- Dietary Uridine Decreases Tumorigenesis in theCurrent developments in nutrition · 2018Article
- Pathway Enrichment Analysis with Networks.Genes · 2017Article
- A hybrid stochastic model of folate-mediated one-carbon metabolism: Effect of the common C677T MTHFR variant on de novo thymidylate biosynthesis.Scientific reports · 2017Article
- Lower serum folate is associated with development and invasiveness of gastric cancer.World journal of gastroenterology · 2014Article
- Network-based Pathway Enrichment Analysis.Proceedings. IEEE International Conference on Bioinformatics and Biomedicine · 2013Article
- Low-dose methotrexate inhibits methionine S-adenosyltransferase in vitro and in vivo.Molecular medicine (Cambridge, Mass.) · 2012Article
- Polymorphisms in serine hydroxymethyltransferase 1 and methylenetetrahydrofolate reductase interact to increase cardiovascular disease risk in humans.The Journal of nutrition · 2011Article
- The methylenetetrahydrofolate reductase C677T mutation induces cell-specific changes in genomic DNA methylation and uracil misincorporation: a possible molecular basis for the site-specific cancer risk modification.International journal of cancer · 2009Article
- Mathematical modeling of folate metabolism: predicted effects of genetic polymorphisms on mechanisms and biomarkers relevant to carcinogenesis.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2008Article
- Methylenetetrahydrofolate reductase C677T genotype affects promoter methylation of tumor-specific genes in sporadic colorectal cancer through an interaction with folate/vitamin B12 status.World journal of gastroenterology · 2008Article
- GNMT expression increases hepatic folate contents and folate-dependent methionine synthase-mediated homocysteine remethylation.Molecular medicine (Cambridge, Mass.)Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The homozygous mutation (677TT) in the methylenetetrahydrofolate reductase (MTHFR) gene reduces enzyme activity and alters cellular folate composition. Previous epidemiological studies reported a potential protective effect of MTHFR677C --> T against acute lymphocytic leukemia and malignant lymphoma, but the mechanism remains to be determined. We investigated the biochemical impacts of MTHFR677C --> T on cellular S-adenosyl methionine (adoMet) synthesis, global DNA methylation, and de novo purine synthesis, all of which are potential regulatory pathways involved in tumorigenesis. Metabolic fluxes of homocysteine remethylation and de novo purine synthesis were compared between Epstein-Barr virus-transformed lymphoblasts expressing MTHFR 677C and MTHFR 677T using stable isotopic tracers and GCMS. MTHFR TT genotype significantly reduced folate-dependent remethylation under folate restriction, reflecting limited methylated folates under folate restriction. Data also suggested increased formylated folate pool and increased purine synthesis when folate is adequate. The impacts of MTHFR 677T polymorphism appeared closely related to folate status, and such alterations may modulate metabolic pathways involved in cancer onset/progression. The advantage of de novo purine synthesis found in the MTHFR TT genotype may account for the protective effect of MTHFR in hematological malignancies. These transformed cells are potential models for studying the consequences of human genetic variation and cancer pathogenesis.
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