AI Article Synopsis
Article Abstract
Patients with acute myeloid leukemia (AML) frequently harbor mutations in genes involved in the DNA (hydroxy)methylation pathway (DNMT3A, TET2, IDH1, and IDH2). In this study, we measured 5-hydroxymethylcytosine (5hmC) levels in 206 clinically and molecularly well-characterized younger adult AML patients (≤60 years) included in the European Organization for Research and Treatment of Cancer/Gruppo Italiano Malattie Ematologiche dell'Adulto (EORTC/GIMEMA) AML-12 06991 clinical trial and correlated the 5hmC levels with mutational status and overall survival (OS). In healthy control cells, 5hmC levels were confined to a narrow range (1.5-fold difference), whereas in AML cells, a much wider range was detected (15-fold difference). We identified 3 5hmC subpopulations in our patient cohort (low, intermediate, and high). The low 5hmC group consisted almost entirely of patients with TET2 or IDH mutations. As expected, TET2 and IDH mutated patients had significantly lower levels of 5hmC compared with patients without mutated TET2 and IDH1/2 (both P < .001). Interestingly, high 5hmC levels correlated with inferior OS (high vs intermediate 5hmC: P = .047, hazard ratio [HR] = 1.81). Multivariate analysis revealed that high 5hmC is an independent poor prognostic indicator for OS (high vs intermediate 5hmC: P = .01, HR = 2.10). This trial was registered at www.clinicaltrials.gov as NCT00004128.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1182/blood-2013-08-518514 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
TET3-facilitated differentiation of human umbilical cord mesenchymal stem cells into oligodendrocyte precursor cells for spinal cord injury recovery.
J Transl Med
December 2024
Department of Orthopaedic Surgery, The First Affiliated Hospital of Harbin Medical University, 2075 Qunli Seventh Avenue, Daoli District, Harbin, 150001, Heilongjiang Province, China.
Background: Spinal cord injury (SCI) inflicts a severe burden on patients and lacks effective treatments. Owing to the poor regenerative capabilities of endogenous oligodendrocyte precursor cells (OPCs) following SCI, there is a growing interest in alternative sources, such as human umbilical cord mesenchymal stem cells (HUCMSCs). TET3 is a key DNA demethylase that plays an important role in neural differentiation, but its role in OPC formation is not well understood.
View Article and Find Full Text PDFThe epigenetic approach of varicocele: a focus on sperm DNA and m6A-RNA methylation.
Hum Reprod Update
December 2024
Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
Background: Varicocele is an abnormal dilation and torsion of the pampiniform venous plexus in the scrotum due to venous reflux, primarily affecting the left side. It affects 15% of men and is a prevalent contributor to male infertility. Varicocele is a complex disorder influenced by genetic, epigenetic, and environmental factors.
View Article and Find Full Text PDFWogonin Inhibits Ovarian Cancer by Activating the AMPK-TET2-5hmC Axis.
Mol Carcinog
December 2024
Department of Biomedical Sciences, National Chung Cheng University, Min-Hsiung, Chia-Yi, Taiwan.
Ovarian cancer is one of the most common gynecologic cancers. In the quest for effective anti-cancer agents, this study explores the effects of wogonin, a naturally occurring flavonoid, on the viability and migration of A2780 and Kuramochi ovarian cancer cells. A2780 and Kuramochi human ovarian cancer cell lines were utilized.
View Article and Find Full Text PDFAlzheimer's disease-specific transcriptomic and epigenomic changes in the tryptophan catabolic pathway.
Alzheimers Res Ther
November 2024
Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences (FHML), Mental Health and Neuroscience Research Institute (MHeNs) and European Graduate School of Neuroscience (EURON), Maastricht University, Maastricht, 6211 LK, the Netherlands.
Background: Neurodegenerative disorders, including Alzheimer's disease (AD), have been linked to alterations in tryptophan (TRP) metabolism. However, no studies to date have systematically explored changes in the TRP pathway at both transcriptional and epigenetic levels. This study aimed to investigate transcriptomic, DNA methylomic (5mC) and hydroxymethylomic (5hmC) changes within genes involved in the TRP and nicotinamide adenine dinucleotide (NAD) pathways in AD, using three independent cohorts.
View Article and Find Full Text PDFVasculogenic skin reprogramming requires TET-mediated gene demethylation in fibroblasts for rescuing impaired perfusion in diabetes.
Nat Commun
November 2024
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Article Synopsis
- - Tissue nanotransfection (TNT) uses plasmids (Etv2, Foxc2, and Fli1) to enhance the formation of vasculogenic fibroblasts (VF) in ischemic skin of mice, promoting new blood vessel growth.
- - In vitro studies show that human dermal fibroblasts exhibit increased endothelial gene expression upon EFF nanoelectroporation, with a link to higher ten-eleven translocase (TET) expression.
- - The study demonstrates that TET activation is crucial for VF development in diabetic ischemic limbs, facilitating blood flow restoration and improved wound healing, especially since TET levels are usually lower in diabetic conditions.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!