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https://www.readbyqxmd.com/read/28938223/the-high-frequency-of-the-u2af1-s34y-mutation-and-its-association-with-isolated-trisomy-8-in-myelodysplastic-syndrome-in-asians-but-not-in-caucasians
#1
Seon Young Kim, Kwantae Kim, Byungjin Hwang, Kyongok Im, Si Nae Park, Jung-Ah Kim, Sang Mee Hwang, Duhee Bang, Dong Soon Lee
Mutational profiles of 153 Korean myelodysplastic syndrome (MDS) patients were investigated. Sequencing of 87 genes presented similar mutational profiles in Korean MDS patients compared with previous reports. The most frequently mutated genes were ASXL1 (22.9%), U2AF1 (16.3%), TP53 (13.7%), RUNX1 (10.5%), TET2 (10.5%), DNMT3A (8.5%), and SRSF2 (8.5%). The U2AF1 mutation frequency was higher, with different frequencies in the mutated sites of U2AF1 (S34Y, 6/25; S34F, 11/25; and Q157P 8/25). The U2AF1 S34Y mutation was strongly associated with isolated trisomy 8 (5/6, 83%) and was characterized by a younger age of MDS onset (median, 39 years)...
September 7, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28927163/frequency-and-clinicopathologic-features-of-runx1-mutations-in-patients-with-acute-myeloid-leukemia-not-otherwise-specified
#2
Eunkyoung You, Young-Uk Cho, Seongsoo Jang, Eul-Ju Seo, Jung-Hee Lee, Je-Hwan Lee, Kyoo-Hyung Lee, Kyung-Nam Koh, Ho Joon Im, Jong Jin Seo, Young-Mi Park, Jong-Keuk Lee, Chan-Jeoung Park
Objectives: To evaluate the frequency and clinicopathologic characteristics of RUNX1 mutations, focusing on patients with acute myeloid leukemia not otherwise specified (AML NOS). Methods: Diagnostic samples from 219 patients with AML NOS were analyzed for RUNX1 mutations using standard polymerase chain reaction and direct sequencing. Results: Thirty-one RUNX1 mutations were detected in 33 (15.1%) patients. Mutations clustered in the Runt homology (61...
July 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28926578/tet-mediated-dna-hydroxymethylation-regulates-retinal-neurogenesis-by-modulating-cell-extrinsic-signaling-pathways
#3
Pawat Seritrakul, Jeffrey M Gross
DNA hydroxymethylation has recently been shown to play critical roles in regulating gene expression and terminal differentiation events in a variety of developmental contexts. However, little is known about its function during eye development. Methylcytosine dioxygenases of the Tet family convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), an epigenetic mark thought to serve as a precursor for DNA demethylation and as a stable mark in neurons. Here, we report a requirement for Tet activity during zebrafish retinal neurogenesis...
September 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28923882/mutational-profiling-of-acute-myeloid-leukemia-with-normal-cytogenetics-in-brazilian-patients-the-value-of-next-generation-sequencing-for-genomic-classification
#4
Thiago Rodrigo de Noronha, Miguel Mitne-Neto, Maria de Lourdes Chauffaille
Karyotype (KT) aberrations are important prognostic factors for acute myeloid leukemia (AML); however, around 50% of cases present normal results. Single nucleotide polymorphism array can detect chromosomal gains, losses or uniparental disomy that are invisible to KT, thus improving patients' risk assessment. However, when both tests are normal, important driver mutations can be detected by the use of next-generation sequencing (NGS). Fourteen adult patients with AML with normal cytogenetics were investigated by NGS for 19 AML-related genes...
September 18, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28915632/decitabine-inhibits-t-cell-proliferation-via-a-novel-tet2-dependent-mechanism-and-exerts-potent-protective-effect-in-mouse-auto-and-allo-immunity-models
#5
Xue Wang, Jun Wang, Yong Yu, Tonghui Ma, Ping Chen, Bing Zhou, Ran Tao
Multiple sclerosis (MS) is an autoimmune disease characterized by the dysregulated immune response including innate and adaptive immune responses. Increasing evidence has proven the importance of epigenetic modification in the progression of MS. Recent studies revealed that low-dose decitabine (Dec, 5-Aza-2'-deoxycytidine), which incorporates into replicating DNA and inhibits DNA methylation, could prevent experimental autoimmune encephalomyelitis (EAE) development by increasing the number of regulatory T cells (Tregs)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28913558/only-setbp1-hotspot-mutations-are-associated-with-refractory-disease-in-myeloid-malignancies
#6
Nils Winkelmann, Vivien Schäfer, Jenny Rinke, Alexander Kaiser, Philipp Ernst, Sebastian Scholl, Andreas Hochhaus, Thomas Ernst
INTRODUCTION: SETBP1 mutations have been established as a diagnostic marker in myeloid malignancies and are associated with inferior survival. Since there is limited data on their clinical impact and stability during disease progression, we sought to investigate the relationship between SETBP1 mutations and disease evolution. METHODS: Bidirectional Sanger sequencing of the SETBP1 gene was performed for 442 unselected patients with World Health Organization (WHO) defined myeloid disorders...
September 14, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28911907/microrna-22-controls-interferon-alpha-production-and-erythroid-maturation-in-response-to-infectious-stress-in-mice
#7
Claudine S Kadmon, Cameron T Landers, Haiyan S Li, Stephanie S Watowich, Antony Rodriguez, Katherine Y King
MicroRNA-22 (miR-22) is a highly conserved microRNA that can regulate cell proliferation, oncogenesis, and cell maturation, especially during stress. In hematopoietic stem cells (HSCs) miR-22 has been reported to be involved in the regulation of key self-renewal factors including Tet2. Recent work demonstrates that miR-22 also participates in regulation of the interferon response, and expression profiling studies suggest that it is variably expressed at different stages in erythroid differentiation. We thus hypothesized that miR-22 regulates maturation of erythroid progenitors during stress hematopoiesis through its interaction with interferon...
September 11, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28889481/a-review-of-the-biologic-and-clinical-significance-of-genetic-mutations-in-angioimmunoblastic-t-cell-lymphoma
#8
REVIEW
Kota Fukumoto, Tran B Nguyen, Shigeru Chiba, Mamiko Sakata-Yanagimoto
Angioimmunoblastic T-cell lymphoma (AITL) is an age-related malignant lymphoma, characterized by immune system-dysregulated symptoms. Recent sequencing studies have clarified the recurrent mutations in ras homology family member A (RHOA) and in genes encoding epigenetic regulators, tet methyl cytosine dioxygenase 2 (TET2), DNA methyl transferase 3 alpha (DNMT3A), and isocitrate dehydrogenase 2, mitochondrial (IDH2), as well as those related to the T-cell receptor signaling pathway in AITL. In this review, we will focus on how this genetic information has changed the understanding of the developmental process of AITL and will in future lead to individualized therapies for AITL patients...
September 10, 2017: Cancer Science
https://www.readbyqxmd.com/read/28887159/integrative-analysis-of-dna-methylation-and-mrna-expression-during-differentiation-of-umbilical-cord-blood-derived-mononuclear-cells-to-endothelial-cells
#9
Yoonjeong Jeong, Yukyung Jun, Jihye Kim, Hyojin Park, Kyu-Sung Choi, Haiying Zhang, Jeong Ae Park, Ja-Young Kwon, Young-Myeong Kim, Sanghyuk Lee, Young-Guen Kwon
Differentiation of umbilical cord blood derived mononuclear cells to endothelial cells is accompanied by massive changes in gene expression. Although methylation and demethylation of DNA likely play crucial roles in regulating gene expression, their interplay during differentiation remains elusive. To address this question, we performed deep sequencing of DNA methylation and mRNA expression to profile global changes in promoter methylation and gene expression during differentiation from mononuclear cells to outgrowing cells...
September 5, 2017: Gene
https://www.readbyqxmd.com/read/28881727/adult-t-cell-leukemia-aggressivenness-correlates-with-loss-of-both-5-hydroxymethylcytosine-and-tet2-expression
#10
Ambroise Marçais, Laetitia Waast, Julie Bruneau, Katia Hanssens, Vahid Asnafi, Philippe Gaulard, Felipe Suarez, Patrice Dubreuil, Antoine Gessain, Olivier Hermine, Claudine Pique
Mutations in TET2, encoding one of the TET members responsible for the conversion of DNA cytosine methylation to hydroxymethylation (5-hmc), have been recently described in Human T-lymphotropic virus type 1-associated adult T-cell leukemia/lymphoma (ATLL). However, neither the amount of genomic 5-hmc in ATLL tumor cells nor TET2 expression has been studied yet. In this study, we analyzed these two parameters as well as the mutational status of TET2 in ATLL patients. By employing a direct in situ approach, we documented that tumor T cells infiltrating lymph nodes exhibit low level of 5-hmc compared to residual normal T cells...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28877089/the-maturation-of-a-neural-hematopoietic-inflammatory-axis-in-cardiovascular-disease
#11
Lotte C A Stiekema, Johan G Schnitzler, Matthias Nahrendorf, Erik S G Stroes
PURPOSE OF REVIEW: Atherogenesis is the result of a complex interplay between lipids and innate immune cells, which are descendants of upstream progenitors residing in hematopoietic organs. In this review, we will discuss recent advances in the connection between hematopoiesis and atherogenesis. RECENT FINDINGS: The relevance of a neural-hematopoietic axis was recently supported by the demonstration of a correlation between metabolic activity in the amygdala and the bone marrow...
September 4, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28875545/targeted-next-generation-sequencing-in-myelodysplastic-syndromes-and-prognostic-interaction-between-mutations-and-ipss-r
#12
Ayalew Tefferi, Terra L Lasho, Mrinal M Patnaik, Lyla Saeed, Mythri Mudireddy, Dame Idossa, Christy Finke, Rhett P Ketterling, Animesh Pardanani, Naseema Gangat
A 27-gene panel was used for next-generation sequencing (NGS) in 179 patients (median age 73 years) with primary myelodysplastic syndromes (MDS); risk distribution according to the revised International Prognostic Scoring System (IPSS-R) was 11% very high, 18% high, 17% intermediate, 38% low and 16% very low. At least one mutation/variant was detected in 147 (82%) patients; 23% harbored three or more mutations/variants. The most frequent mutations/variants included ASXL1 (30%), TET2 (25%), SF3B1 (20%), U2AF1 (16%), SRSF2 (16%), TP53 (13%), RUNX1 (11%) and DNMT3A (10%)...
September 5, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28870206/3-6-dihydroxyflavone-regulates-microrna-34a-through-dna-methylation
#13
Xiaoli Peng, Hui Chang, Junli Chen, Qianyong Zhang, Xiaoping Yu, Mantian Mi
BACKGROUND: Breast cancer is the common cancer in China. In previous study, we determined that 3,6-dihydroxyflavone (3,6-DHF) increases miR-34a significantly in breast carcinogenesis, but the mechanism remains unclear. METHODS: We used qRT-PCR to analyze miR-34a and ten-eleven translocation (TET)1, TET2, TET3 levels in breast cancer cells. With a cellular breast carcinogenesis model and an experimental model of carcinogenesis in rats, TET1 levels were evaluated by western blot analysis and immunofluorescence...
September 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28864482/ascorbate-depletion-reduces-tet2-activity-to-accelerate-leukemogenesis
#14
(no author information available yet)
Elevated ascorbate levels maintain TET2 activity in HSCs and decline with differentiation.
September 1, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28855337/an-epigenetic-switch-repressing-tet1-in-gonadotropes-activates-the-reproductive-axis
#15
Yahav Yosefzon, Cfir David, Anna Tsukerman, Lilach Pnueli, Sen Qiao, Ulrich Boehm, Philippa Melamed
The TET enzymes catalyze conversion of 5-methyl cytosine (5mC) to 5-hydroxymethyl cytosine (5hmC) and play important roles during development. TET1 has been particularly well-studied in pluripotent stem cells, but Tet1-KO mice are viable, and the most marked defect is abnormal ovarian follicle development, resulting in impaired fertility. We hypothesized that TET1 might play a role in the central control of reproduction by regulating expression of the gonadotropin hormones, which are responsible for follicle development and maturation and ovarian function...
August 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28842406/vitamin-c-restores-tet2-activity-in-tet2-deficient-leukemia
#16
(no author information available yet)
TET2 restoration promotes DNA demethylation and differentiation to suppress leukemic progression.
August 25, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28826859/tet2-restrains-inflammatory-gene-expression-in-macrophages
#17
Alyssa H Cull, Brooke Snetsinger, Rena Buckstein, Richard A Wells, Michael J Rauh
Tet methylcytosine dioxygenase 2 (TET2) is one of the earliest and most frequently mutated genes in clonal hematopoiesis of aging (CHIP) and myeloid cancers, including myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). TET2 catalyzes the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine, leading to DNA demethylation. TET2 also affects transcription by recruiting histone modifiers. Inactivating TET2 mutations cause epigenetic dysregulation, clonal hematopoietic stem cell dominance and monocytic lineage skewing...
August 18, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28825709/ascorbate-regulates-haematopoietic-stem-cell-function-and-leukaemogenesis
#18
Michalis Agathocleous, Corbin E Meacham, Rebecca J Burgess, Elena Piskounova, Zhiyu Zhao, Genevieve M Crane, Brianna L Cowin, Emily Bruner, Malea M Murphy, Weina Chen, Gerald J Spangrude, Zeping Hu, Ralph J DeBerardinis, Sean J Morrison
Stem cell fate can be influenced by metabolite levels in culture but it is unknown whether physiological variations in metabolite levels in normal tissues regulate stem cell function in vivo. We developed a metabolomics method for analysis of rare cell populations isolated directly from tissues and used it to compare haematopoietic stem cells (HSCs) to restricted haematopoietic progenitors. Each haematopoietic cell type had a distinct metabolic signature. Human and mouse HSCs had unusually high levels of ascorbate, which declined with differentiation...
August 21, 2017: Nature
https://www.readbyqxmd.com/read/28813683/tet2-regulates-mast-cell-differentiation-and-proliferation-through-catalytic-and-non-catalytic-activities
#19
Sara Montagner, Cristina Leoni, Stefan Emming, Giulia Della Chiara, Chiara Balestrieri, Iros Barozzi, Viviana Piccolo, Susan Togher, Myunggon Ko, Anjana Rao, Gioacchino Natoli, Silvia Monticelli
No abstract text is available yet for this article.
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813659/the-dna-methylcytosine-dioxygenase-tet2-sustains-immunosuppressive-function-of-tumor-infiltrating-myeloid-cells-to-promote-melanoma-progression
#20
Wen Pan, Shu Zhu, Kun Qu, Katrina Meeth, Jijun Cheng, Kaixin He, Hongdi Ma, Yan Liao, Xizhi Wen, Christine Roden, Zuzana Tobiasova, Zheng Wei, Jun Zhao, Jun Liu, Ji Zheng, Bo Guo, Sajid A Khan, Marcus Bosenberg, Richard A Flavell, Jun Lu
Ten-Eleven-Translocation-2 (Tet2) is a DNA methylcytosine dioxygenase that functions as a tumor suppressor in hematopoietic malignancies. We examined the role of Tet2 in tumor-tissue myeloid cells and found that Tet2 sustains the immunosuppressive function of these cells. We found that Tet2 expression is increased in intratumoral myeloid cells both in mouse models of melanoma and in melanoma patients and that this increased expression is dependent on an IL-1R-MyD88 pathway. Ablation of Tet2 in myeloid cells suppressed melanoma growth in vivo and shifted the immunosuppressive gene expression program in tumor-associated macrophages to a proinflammatory one, with a concomitant reduction of the immunosuppressive function...
August 15, 2017: Immunity
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