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T-ALL epigenetics

Mark A Pianka, Alec T McIntosh, Sahaj D Patel, Pegah R Bakhshi, Mira Jung
Genetic imprinting is the process of epigenetic labelling or silencing of particular genes, based on the maternal or paternal origin of the gene, in a heritable pattern. The incidence of imprinting disorders has become a growing concern due to the potential association between these congenital syndromes and assisted reproductive technologies (ARTs). This review presents a general summary of the imprinting process as well as the current knowledge surrounding the genetic and epigenetic underpinnings of the most prevalent imprinting disorders: Beckwith-Wiedemann syndrome (BWS), Silver-Russell syndrome (SRS), Prader-Willi syndrome (PWS), and Angelman syndrome (AS)...
2018: American Journal of Stem Cells
Christopher Chin, Emma S Lunking, Macarena de la Fuente, Nagi G Ayad
Glioblastoma Multiforme (GBM) is the most common malignant primary brain tumor. Despite aggressive multimodality treatment it remains one of the most challenging and intractable cancers (1]. While current standard of care treatment for GBM is maximal safe surgical resection, systemic chemotherapy with Temozolimide (TMZ), and radiation therapy, the current prognosis of GBM patients remains poor, with a median overall survival of 12-15 months (2, 3). Therefore, other treatments are needed to provide better outcomes for GBM patients...
2018: Frontiers in Oncology
Trevor T Nyakudya, Emmanuel Mukwevho, Kennedy H Erlwanger
Background: Consumption of fructose-rich diets has been implicated in the increasing global prevalence of metabolic syndrome (MetS). Interventions during periods of early ontogenic developmental plasticity can cause epigenetic changes which program metabolism for positive or negative health benefits later in life. The phytochemical oleanolic acid (OA) possesses anti-diabetic and anti-obesity effects. We investigated the potential protective effects of neonatal administration of OA on the subsequent development of high fructose diet-induced metabolic dysfunction in rats...
2018: Nutrition & Metabolism
Vicki E Maltby, Rodney A Lea, Moira C Graves, Katherine A Sanders, Miles C Benton, Lotti Tajouri, Rodney J Scott, Jeannette Lechner-Scott
Multiple Sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system. The inflammatory process in MS is driven by both T and B cells and current therapies are targeted to each of these cell types. Epigenetic mechanisms may provide a valuable link between genes and environment. DNA methylation is the best studied epigenetic mechanism and is recognized as a potential contributor to MS risk. The objective of this study was to identify DNA methylation changes associated with MS in CD19+ B-cells...
November 27, 2018: Scientific Reports
Yi Fang, Jinlong Zhang, Yihai Li, Xiaofei Guo, Junjie Li, Rongzhen Zhong, Xiaosheng Zhang
Physical damage and oxidative stress may occur in prepubertal cumulus cells, due to insufficient glutathione synthesis. To determine potential epigenetic mechanisms related to antioxidant effects of melatonin on ovine prepubertal cumulus cells, 30 lambs, 4-wk-old were randomly allocated into two groups: a control (C, n=20) group and a melatonin (M, n=10) group given a subcutaneous implant containing 18mg melatonin. All lambs were superovulated (250 IU FSH and 250 IU eCG). Cumulus cells from germinal vesicle stage cumulus oocyte complexes (COCs) were collected by ovarian follicular aspiration and dissociated with hyaluronidase...
November 22, 2018: Free Radical Biology & Medicine
Priyanka Parmar, Estelle Lowry, Giovanni Cugliari, Matthew Suderman, Rory Wilson, Ville Karhunen, Toby Andrew, Petri Wiklund, Matthias Wielscher, Simonetta Guarrera, Alexander Teumer, Benjamin Lehne, Lili Milani, Niek de Klein, Pashupati P Mishra, Phillip E Melton, Pooja R Mandaviya, Silva Kasela, Jana Nano, Weihua Zhang, Yan Zhang, Andre G Uitterlinden, Annette Peters, Ben Schöttker, Christian Gieger, Denise Anderson, Dorret I Boomsma, Hans J Grabe, Salvatore Panico, Jan H Veldink, Joyce B J van Meurs, Leonard van den Berg, Lawrence J Beilin, Lude Franke, Marie Loh, Marleen M J van Greevenbroek, Matthias Nauck, Mika Kähönen, Mikko A Hurme, Olli T Raitakari, Oscar H Franco, P Eline Slagboom, Pim van der Harst, Sonja Kunze, Stephan B Felix, Tao Zhang, Wei Chen, Trevor A Mori, Amelie Bonnefond, Bastiaan T Heijmans, Taulant Muka, Jaspal S Kooner, Krista Fischer, Melanie Waldenberger, Philippe Froguel, Rae-Chi Huang, Terho Lehtimäki, Wolfgang Rathmann, Caroline L Relton, Giuseppe Matullo, Hermann Brenner, Niek Verweij, Shengxu Li, John C Chambers, Marjo-Riitta Järvelin, Sylvain Sebert
BACKGROUND: DNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health. METHODS: We meta-analysed the association between DNA methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n = 18,212)...
November 12, 2018: EBioMedicine
V Lac, L Verhoef, R Aguirre-Hernandez, T M Nazeran, B Tessier-Cloutier, T Praetorius, N L Orr, H Noga, A Lum, J Khattra, L M Prentice, D Co, M Köbel, V Mijatovic, A F Lee, J Pasternak, M C Bleeker, B Krämer, S Y Brucker, F Kommoss, S Kommoss, H M Horlings, P J Yong, D G Huntsman, M S Anglesio
STUDY QUESTION: Does incisional endometriosis (IE) harbor somatic cancer-driver mutations? SUMMARY ANSWER: We found that approximately one-quarter of IE cases harbor somatic-cancer mutations, which commonly affect components of the MAPK/RAS or PI3K-Akt-mTor signaling pathways. WHAT IS KNOWN ALREADY: Despite the classification of endometriosis as a benign gynecological disease, it shares key features with cancers such as resistance to apoptosis and stimulation of angiogenesis and is well-established as the precursor of clear cell and endometrioid ovarian carcinomas...
November 14, 2018: Human Reproduction
Dean E Schraufnagel, John Balmes, Clayton T Cowl, Sara De Matteis, Soon-Hee Jung, Kevin Mortimer, Rogelio Perez-Padilla, Mary B Rice, Horacio Riojas-Rodroguez, Akshay Sood, George D Thurston, Teresa To, Anessa Vanker, Donald J Wuebbles
Air pollution poses a great environmental risk to health. Outdoor fine particulate matter (PM2.5 ) exposure is the fifth leading risk factor for death in the world, accounting for 4.2 million deaths and more than a hundred million disability-adjusted-life-years lost according to the Global Burden of Disease Report. The World Health Organization attributes 3.8 million additional deaths to Indoor air pollution. Air pollution can harm acutely, usually manifested by respiratory or cardiac symptoms, as well as chronically, potentially affecting every organ in the body...
November 9, 2018: Chest
Elena Chiappini, Martina Bianconi, Annalisa Dalzini, Maria Raffaella Petrara, Luisa Galli, Carlo Giaquinto, Anita De Rossi
BACKGROUND: Premature aging and related diseases have been documented in HIV-infected adults. Data are now emerging also regarding accelerated aging process in HIV-infected children. METHODS: A narrative review was performed searching studies on PubMed published in English language in 2004-2017, using appropriate key words, including "aging", "children", "HIV", "AIDS", "immunosenescence", "pathogenesis", "clinical conditions"...
November 11, 2018: Aging
Haichuan Zhu, Liuzhen Zhang, Yilin Wu, Bingjie Dong, Weilong Guo, Mei Wang, Lu Yang, Xiaoying Fan, Yuliang Tang, Ningshu Liu, Xiaoguang Lei, Hong Wu
Leukemia stem cells (LSCs) are regarded as the origins and key therapeutic targets of leukemia, but limited knowledge is available on the key determinants of LSC 'stemness'. Using single-cell RNA-seq analysis, we identify a master regulator, SPI1, the LSC-specific expression of which determines the molecular signature and activity of LSCs in the murine Pten -null T-ALL model. Although initiated by PTEN-controlled β-catenin activation, Spi1 expression and LSC 'stemness' are maintained by a β-catenin-SPI1-HAVCR2 regulatory circuit independent of the leukemogenic driver mutation...
November 9, 2018: ELife
Paulina Richter-Pechańska, Joachim B Kunz, Beat Bornhauser, Caroline von Knebel Doeberitz, Tobias Rausch, Büşra Erarslan-Uysal, Yassen Assenov, Viktoras Frismantas, Blerim Marovca, Sebastian M Waszak, Martin Zimmermann, Julia Seemann, Margit Happich, Martin Stanulla, Martin Schrappe, Gunnar Cario, Gabriele Escherich, Kseniya Bakharevich, Renate Kirschner-Schwabe, Cornelia Eckert, Martina U Muckenthaler, Jan O Korbel, Jean-Pierre Bourquin, Andreas E Kulozik
We compared 24 primary pediatric T-cell acute lymphoblastic leukemias (T-ALL) collected at the time of initial diagnosis and relapse from 12 patients and 24 matched patient-derived xenografts (PDXs). DNA methylation profile was preserved in PDX mice in 97.5% of the promoters (ρ = 0.99). Similarly, the genome-wide chromatin accessibility (ATAC-Seq) was preserved remarkably well (ρ = 0.96). Interestingly, both the ATAC regions, which showed a significant decrease in accessibility in PDXs and the regions hypermethylated in PDXs, were associated with immune response, which might reflect the immune deficiency of the mice and potentially the incomplete interaction between murine cytokines and human receptors...
November 2, 2018: EMBO Molecular Medicine
Charles G Mullighan
Hematopoietic progenitors undergo marked shifts during transition from fetal to postnatal life, and the implication of these changes for the cell-of-origin of childhood leukemia are unclear. In this issue of Cell Stem Cell, Giambra et al. (2018) show that epigenetically regulated IGF1 signaling regulates the ability of fetal-liver- or bone-marrow-derived cells to initiate T-ALL.
November 1, 2018: Cell Stem Cell
Jean-Jacques Michaille, Hamdy Awad, Emily C Fortman, Alexander A Efanov, Esmerina Tili
MicroRNAs are small non-coding RNAs that modulate gene expression either directly, by impairing the stability and/or translation of transcripts that contain their specific target sequence, or indirectly through the targeting of transcripts that encode transcription factors, factors implicated in signal transduction pathways, or epigenetic regulators. Abnormal expression of microRNAs has been found in nearly all types of pathologies, including cancers. MiR-155 has been the first microRNA to be implicated in the regulation of the innate and adaptative immune responses, and its expression is either increased or decreased in a variety of liquid and solid malignancies...
November 1, 2018: Genes, Chromosomes & Cancer
Atsushi Tanaka, Patrick S C Leung, M Eric Gershwin
The discovery of mitochondrial autoantigens recognized by antimitochondrial antibodies (AMAs) in 1987 marked the dawn of a new era in primary biliary cholangitis (PBC) research. Since then, there has been substantial progress in our understanding of PBC partly bestowed by the development of innovative technologies in molecular biology, immunology, and genetics. Here, we review this evolutionary progress in understanding PBC. We now recognize that the epitopes of AMAs, CD4+ , and CD8+ T cells are all mapped to the same region of the inner lipoyl domain of pyruvate dehydrogenase complex E2 subunit (PDC-E2), and that intrahepatic biliary epithelial cells (BECs) are exclusively targeted in PBC...
June 2018: Best Practice & Research. Clinical Gastroenterology
B-H Bin, S-H Lee, J Bhin, T Irié, S Kim, J Seo, K Mishima, T R Lee, D Hwang, T Fukada, E-G Cho
BACKGROUND: The skin is the first organ that manifests changes in response to zinc deficiency. However, the molecular mechanism underlying how zinc is involved in skin homeostasis, especially in its epigenetic regulation, is largely unknown. OBJECTIVES: In this study, we demonstrate the importance of zinc levels and the zinc transporter ZIP10 in the epigenetic maintenance of human epidermal homeostasis. METHODS: Adult human skin, including skin appendages were stained with anti-ZIP10 antibody...
October 19, 2018: British Journal of Dermatology
Elizabeth M Curtis, Nevena Krstic, Eloïse Cook, Stefania D'Angelo, Sarah R Crozier, Rebecca J Moon, Robert Murray, Emma Garratt, Paula Costello, Jane Cleal, Brogan Ashley, Nicholas J Bishop, Stephen Kennedy, Aris T Papageorghiou, Inez Schoenmakers, Robert Fraser, Saurabh V Gandhi, Ann Prentice, M Kassim Javaid, Hazel M Inskip, Keith M Godfrey, Christopher G Bell, Karen A Lillycrop, Cyrus Cooper, Nicholas C Harvey
We have previously demonstrated inverse associations between maternal 25(OH)-vitamin D status and perinatal DNA methylation at the retinoid-X-receptor-alpha (RXRA) locus and between RXRA methylation and offspring bone mass. We therefore used an existing randomised trial to test the hypothesis that maternal gestational vitamin D supplementation would lead to reduced perinatal RXRA locus DNA methylation. The Maternal Vitamin D Osteoporosis Study (MAVIDOS) was a multicentre, double-blind, randomised, placebo-controlled trial of 1000IU/day cholecalciferol or matched placebo from 14 weeks' gestation until delivery...
October 15, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
K Cui, B Wang, T Ma, B W Si, N F Zhang, Y Tu, Q Y Diao
The present study aimed to investigate the compensatory effect of early protein restriction followed by a realimentation on growth performance of lamb and to explore the transcriptomic changes in liver. Thirty-two lambs with an initial birth weight of 2.3 ± 0.20 kg that were weaned on day 15 were randomly divided into two groups. The lambs were fed a basal diet with normal protein level (NPL, protein level in the milk replacer and starter, 25 and 21%, respectively) or low protein level (LPL, protein level in the milk replacer and starter, 19 and 15%, respectively) from 15 to 60 d, after which all lambs consumed the same diet with a normal protein level from 61 to 90 d...
October 12, 2018: Scientific Reports
Stella Aslibekyan, Laura Almasy, Michael A Province, Devin M Absher, Donna K Arnett
GAW20 provided participants with an opportunity to comprehensively examine genetic and epigenetic variation among related individuals in the context of drug treatment response. GAW20 used data from 188 families ( N  = 1105) participating in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study ( identifier NCT00083369), which included CD4+ T-cell DNA methylation at 463,995 cytosine-phosphate-guanine (CpG) sites measured before and after a 3-week treatment with fenofibrate, single-nucleotide variation at 906,600 loci, metabolic syndrome components ascertained before and after the drug intervention, and relevant covariates...
2018: BMC Proceedings
Aldi T Kraja, Ping An, Petra Lenzini, Shiou J Lin, Christine Williams, James E Hicks, E Warwick Daw, Michael A Province
The GAW20 simulation data set is based upon the companion Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study fenofibrate clinical trial data set that forms the real data example for GAW20. The simulated data problem consists of 200 simulated replications of what might happen if we were to repeat the GOLDN clinical trial 200 independent times, for these exact same subjects, but using a new fictitious drug (called "genomethate") that has a pharmaco-epigenetic effect on triglyceride response...
2018: BMC Proceedings
Paras Garg, Ricky S Joshi, Corey Watson, Andrew J Sharp
While population studies have resulted in detailed maps of genetic variation in humans, to date there are few robust maps of epigenetic variation. We identified sites containing clusters of CpGs with high inter-individual epigenetic variation, termed Variably Methylated Regions (VMRs) in five purified cell types. We observed that VMRs occur preferentially at enhancers and 3' UTRs. While the majority of VMRs have high heritability, a subset of VMRs within the genome show highly correlated variation in trans, forming co-regulated networks that have low heritability, differ between cell types and are enriched for specific transcription factor binding sites and biological pathways of functional relevance to each tissue...
October 2018: PLoS Genetics
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