Global methylation in relation to methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia

  title={Global methylation in relation to methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia},
  author={Natanja Oosterom and Pieter H Griffioen and Marissa A. H. den Hoed and Rob Pieters and Robert de Jonge and Wim J. E. Tissing and Marry M M van den Heuvel-Eibrink and Sandra G. Heil},
  journal={PLoS ONE},
Background Children with acute lymphoblastic leukemia (ALL) often suffer from toxicity of chemotherapeutic drugs such as Methotrexate (MTX). Previously, we reported that 20% of patients receiving high-dose MTX developed oral mucositis. MTX inhibits folate metabolism, which is essential for DNA methylation. We hypothesize that MTX inhibits DNA methylation, which results into adverse effects. We studied DNA methylation markers during high-dose methotrexate treatment in pediatric acute… Expand
6 Citations
Higher baseline global leukocyte DNA methylation is associated with MTX non-response in early RA patients
Results show that higher baseline global DNA methylation in treatment naïve eRA patients is associated with decreased clinical response after 3 months of treatment of e RA patients and can be further evaluated as a predictor for MTX therapy non-response. Expand
Incidence and risk factors for oral mucositis in pediatric patients receiving chemotherapy
Chemotherapy protocols using high-dose methotrexate, MTX-HD associated with doxorubicin and cyclophosphamide, and MTx-HD and cyclphosphamide a have higher incidence of severe grades of OM, and other toxicities such as hematological, hepatic, and renal also developed in patients with OM. Expand
Oral Health, Caries Risk Profiles, and Oral Microbiome of Pediatric Patients with Leukemia Submitted to Chemotherapy
  • Yan Wang, Xinyi Zeng, +4 authors J. Zou
  • Medicine
  • BioMed research international
  • 2021
All patients receiving chemotherapy demonstrated compromised oral health, high caries risk, alteration of caries-related factors, and dysbiosis of oral microbiota in pediatric patients with ALL. Expand
Effects of methotrexate combined with leflunomide on efficacy, joint function and inflammatory factors in patients with rheumatoid arthritis
Objective: To investigate the effect of methotrexate (MTX) combined with leflunomide (LEF) in the treatment of rheumatoid arthritis (RA). Methods: A total of 100 patients with RA who were admitted toExpand
Auger electron therapy of glioblastoma using [125I]5-iodo-2'-deoxyuridine and concomitant chemotherapy - Evaluation of a potential treatment strategy.
Overall, the study revealed a higher incorporation and therapeutic effect of [125I]I-UdR when GBM cells were co-treated with F- UdR compared to MTX, and if the co-treatment should be given in a neoadjuvant or adjuvant setting. Expand


Genetic and metabolic determinants of methotrexate-induced mucositis in pediatric acute lymphoblastic leukemia
Methotrexate (MTX) is an effective and toxic chemotherapeutic drug in the treatment of pediatric acute lymphoblastic leukemia and only patients with the wild-type variant of rs7317112 SNP in the ABCC4 gene had more mucositis, and there was no evidence that erythrocyte folate levels mediate in the association between the rs73 17112 and mucositIS. Expand
DNA hypomethylation in inflammatory arthritis: reversal with methotrexate.
It is indicated that inflammatory arthritis is associated with genomic DNA hypomethylation that is reversed with methotrexate, and future studies using a larger number of subjects are warranted to confirm these findings. Expand
Methylation level of CpG islands in GGH gene promoter in pediatric acute leukemia
Either methylation of CpG1 or hypermethylation ofCpG2 in GGH promoter region can significantly reduce GGH mRNA expression in pediatric patients with acute leukemia, which can improve the response to treatment. Expand
DNA Methylation Events as Markers for Diagnosis and Management of Acute Myeloid Leukemia and Myelodysplastic Syndrome
It is reported that distinct changes in DNA methylation may alter gene function and drive malignant cellular transformation during several stages of leukemogenesis, which justifies its use as a biomarker for disease onset and progression. Expand
Association of somatic DNA methylation variability with progression-free survival and toxicity in ovarian cancer patients.
This is the first study linking DNA methylation variability in WBC to clinical outcomes for any tumour type; the data generated on novel prognostic and pharmacoepigeneticDNA methylation biomarkers in the circulation now need independent further evaluation. Expand
Low-Dose Methotrexate Inhibits Methionine S-Adenosyltransferase In Vitro and In Vivo
It is found that methionine or folate supplementation greatly improved S-adenosylmethionine in folate-depleted cells but not in cells preexposed to methotrexate, which raises concerns on perturbed methylation reactions in humans on low-dose metotrexate. Expand
Long-term results of Dutch Childhood Oncology Group studies for children with acute lymphoblastic leukemia from 1984 to 2004
It is concluded that the chemotherapy-only approach in children with ALL in Total Therapy-based strategies and BFM-backbone treatment does not jeopardize survival and preserves cognitive functioning. Expand
Successful Therapy Reduction and Intensification for Childhood Acute Lymphoblastic Leukemia Based on Minimal Residual Disease Monitoring: Study ALL10 From the Dutch Childhood Oncology Group.
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Assessment of global DNA methylation in peripheral blood cell subpopulations of early rheumatoid arthritis before and after methotrexate
Global DNA hypomethylation in patients with RA is confirmed with specificity for some blood cell subpopulations and their reversal with methotrexate treatment, suggesting the possibility of regulation at this level. Expand
Changes in plasma methionine and total homocysteine levels in patients receiving methotrexate infusions.
Investigation of the effects of moderate dose to very high dose methotrexate on methionine and total homocysteine as reflections of metotrexate induced intracellular events found changes in homocy steine and methionines may reflect biological effects of methot Rexate that may predict cytotoxicity of metHotrexate. Expand