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https://www.readbyqxmd.com/read/28433419/disconnect-between-alcohol-induced-alterations-in-chromatin-structure-and-gene-transcription-in-a-mouse-embryonic-stem-cell-model-of-exposure
#1
Kylee J Veazey, Haiqing Wang, Yudhishtar S Bedi, William M Skiles, Richard Cheng-An Chang, Michael C Golding
Alterations to chromatin structure induced by environmental insults have become an attractive explanation for the persistence of exposure effects into subsequent life stages. However, a growing body of work examining the epigenetic impact that alcohol and other drugs of abuse exert consistently notes a disconnection between induced changes in chromatin structure and patterns of gene transcription. Thus, an important question is whether perturbations in the 'histone code' induced by prenatal exposures to alcohol implicitly subvert gene expression, or whether the hierarchy of cellular signaling networks driving development is such that they retain control over the transcriptional program...
January 11, 2017: Alcohol
https://www.readbyqxmd.com/read/28424163/clinical-significance-of-somatic-mutation-in-unexplained-blood-cytopenia
#2
Luca Malcovati, Anna Gallì, Erica Travaglino, Ilaria Ambaglio, Ettore Rizzo, Elisabetta Molteni, Chiara Elena, Virginia Valeria Ferretti, Silvia Catricalà, Elisa Bono, Gabriele Todisco, Antonio Bianchessi, Elisa Rumi, Silvia Zibellini, Daniela Pietra, Emanuela Boveri, Clara Camaschella, Daniela Toniolo, Elli Papaemmanuil, Seishi Ogawa, Mario Cazzola
Unexplained blood cytopenias, in particular anemia, are often found in older persons. The relationship between these cytopenias and myeloid neoplasms like myelodysplastic syndromes is currently poorly defined. We studied a prospective cohort of patients with unexplained cytopenia with the aim to estimate the predictive value of somatic mutations for identifying subjects with, or at risk of developing a myeloid neoplasm. The study included a learning cohort of 683 consecutive patients investigated for unexplained cytopenia, and a validation cohort of 190 patients referred for suspected myeloid neoplasm...
April 19, 2017: Blood
https://www.readbyqxmd.com/read/28419183/comparison-of-the-mutational-profiles-of-primary-myelofibrosis-polycythemia-vera-and-essential-thrombocytosis
#3
Jinming Song, Mohammad Hussaini, Hailing Zhang, Haipeng Shao, Dahui Qin, Xiaohui Zhang, Zhenjun Ma, Syeda Mahrukh Hussnain Naqvi, Ling Zhang, Lynn C Moscinski
Objectives: To compare the mutational profiles of patients with primary myelofibrosis (PMF), polycythemia vera (PV), and essential thrombocytosis (ET). Methods: Next-generation sequencing results of 75 cases of PMF, 33 cases of PV, and 27 cases of ET were compared. Results: Mutation rates of ASXL1 and SRSF2 were significantly higher in PMF than in PV or ET. ASXL1 mutations appeared to be more frequently associated with risk of transformation to acute myeloid leukemia than JAK2 or TET2 mutations...
April 15, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28416650/epigenetic-regulator-cxxc5-recruits-dna-demethylase-tet2-to-regulate-tlr7-9-elicited-ifn-response-in-pdcs
#4
Shixin Ma, Xiaoling Wan, Zihou Deng, Lei Shi, Congfang Hao, Zhenyuan Zhou, Chun Zhou, Yiyuan Fang, Jinghua Liu, Jing Yang, Xia Chen, Tiantian Li, Aiping Zang, Shigang Yin, Bin Li, Joel Plumas, Laurence Chaperot, Xiaoming Zhang, Guoliang Xu, Lubin Jiang, Nan Shen, Sidong Xiong, Xiaoming Gao, Yan Zhang, Hui Xiao
TLR7/9 signals are capable of mounting massive interferon (IFN) response in plasmacytoid dendritic cells (pDCs) immediately after viral infection, yet the involvement of epigenetic regulation in this process has not been documented. Here, we report that zinc finger CXXC family epigenetic regulator CXXC5 is highly expressed in pDCs, where it plays a crucial role in TLR7/9- and virus-induced IFN response. Notably, genetic ablation of CXXC5 resulted in aberrant methylation of the CpG-containing island (CGI) within the Irf7 gene and impaired IRF7 expression in steady-state pDCs...
April 17, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28409505/dynamic-changes-in-dna-demethylation-in-the-tree-shrew-tupaia-belangeri-chinensis-brain-during-postnatal-development-and-aging
#5
Shu Wei, Hai-Rong Hua, Qian-Quan Chen, Ying Zhang, Fei Chen, Shu-Qing Li, Fan Li, Jia-Li Li
Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5-hydroxymethylcytosine (5hmC) ten-eleven translocation (TET) enzyme-mediated active DNA demethylation products were dynamically changed and involved in postnatal brain development and aging in tree shrews (Tupaia belangeri chinensis). The levels of 5hmC in multiple anatomic structures showed a gradual increase throughout postnatal development, whereas a significant decrease in 5hmC was found in several brain regions in aged tree shrews, including in the prefrontal cortex and hippocampus, but not the cerebellum...
March 18, 2017: Zoological Research
https://www.readbyqxmd.com/read/28407691/tet2-and-meg3-promoter-methylation-is-associated-with-acute-myeloid-leukemia-in-a-hainan-population
#6
Hongxia Yao, Mengling Duan, Lie Lin, Congming Wu, Xiangjun Fu, Hua Wang, Li Guo, Wenting Chen, Li Huang, Dan Liu, Ruo Rao, Shuwen Wang, Yipeng Ding
The promoter of MEG3, which encodes the long non-coding RNA (lncRNA) MEG3, is often hypermethylated in acute myeloid leukemia (AML). Additionally, the Tet methylcytosine dioxygenase 2 gene (TET2) is frequently inactivated, which can lead to impaired DNA methylation and promote AML development. We examined the association between TET2 and MEG3 promoter hypermethylation in Hainan patients with AML. The expression of MEG3, TET2, miR-22-3p, and miR-22-5p was assessed in bone marrow samples from AML patients and healthy controls using real-time quantitative PCR...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28400619/dysfunction-of-the-wt1-meg3-signaling-promotes-aml-leukemogenesis-via-p53-dependent-and-independent-pathways
#7
Y Lyu, J Lou, Y Yang, J Feng, Y Hao, S Huang, L Yin, J Xu, D Huang, B Ma, D Zou, Y Wang, Y Zhang, B Zhang, P Chen, K Yu, Ew-F Lam, X Wang, Q Liu, J Yan, B Jin
Long non-coding RNAs (lncRNAs) play a pivotal role in tumorigenesis, exemplified by the recent finding that lncRNA MEG3 inhibits tumor growth in a p53-dependent manner. Acute myeloid leukemia (AML) is the most common malignant myeloid disorder in adults, and TP53 mutations or loss are frequently detected in patients with therapy-related AML or AML with complex karyotype. Here, we reveal that MEG3 is significantly down-regulated in AML and suppresses leukemogenesis in not only a p53-dependent, but also a p53-independent manner...
April 12, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28394181/a-novel-recurrent-copy-number-loss-region-on-6q23-3-in-mds-related-myeloid-malignancy-patients-with-stable-survival-conditions
#8
Kun Chi, Yang Li, Lan Xu, Xuefeng Wang
Metaphase cytogenetics (MC) karyotyping is a fundamental way to approach cytogenetic pathogenesis of MDS-related myeloid malignancies. However, in some patients, the results are normal while the patients often show discrepancies in survival conditions. To explain this question, we analyzed CytoScan™ HD array results of 20 MC-normal/failure patients who were followed up for three years. Exon sequencing was performed in genes RUNX1, TP53, ASXL1, and TET2. The array enabled the detection of additional aberrations in 16 (80%) patients...
April 10, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28389256/impact-of-molecular-genetics-on-outcome-in-myelofibrosis-patients-after-allogeneic-stem-cell-transplantation
#9
Nicolaus Kröger, Victoria Panagiota, Anita Badbaran, Tatjana Zabelina, Ioanna Triviai, Michelle Maria Araujo Cruz, Rabia Shahswar, Francis Ayuk, Marten Gehlhaar, Christine Wolschke, Robin Bollin, Carolin Walter, Martin Dugas, Lutz Wiehlmann, Ulrich Lehmann, Christian Koenecke, Anuhar Chaturvedi, Haefaa Alchalby, Michael Stadler, Matthias Eder, Max Christopeit, Gudrun Göhring, Michael Koenigsmann, Brigitte Schlegelberger, Hans-Heinrich Kreipe, Arnold Ganser, Carol Stocking, Boris Fehse, Felicitas Thol, Michael Heuser
Molecular genetics may influence outcome for patients with myelofibrosis. To determine the impact of molecular genetics on outcome after allogeneic stem cell transplantation, we screened 169 patients with primary myelofibrosis (n = 110), post-ET/PV myelofibrosis (n = 46), and myelofibrosis in transformation (n = 13) for mutations in 16 frequently mutated genes. The most frequent mutation was JAK2V617F (n = 101) followed by ASXL1 (n = 49), calreticulin (n = 34), SRSF2 (n = 16), TET2 (n = 10), U2AF1 (n = 11), EZH2 (n = 7), MPL (n = 6), IDH2 (n = 5), IDH1 (n = 4), and CBL (n = 1)...
April 4, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28388552/myelodysplastic-syndromes-advantages-of-a-combined-cytogenetic-and-molecular-diagnostic-workup
#10
Elena Ciabatti, Angelo Valetto, Veronica Bertini, Maria Immacolata Ferreri, Alice Guazzelli, Susanna Grassi, Francesca Guerrini, Iacopo Petrini, Maria Rita Metelli, Maria Adelaide Caligo, Simona Rossi, Sara Galimberti
In this study we present a new diagnostic workup for the myelodysplastic syndromes (MDS) including FISH, aCGH, and somatic mutation assays in addition to the conventional cytogenetics (CC). We analyzed 61 patients by CC, FISH for chromosome 5, 7, 8 and PDGFR rearrangements, aCGH, and PCR for ASXL1, EZH2, TP53, TET2, RUNX1, DNMT3A, SF3B1 somatic mutations. Moreover, we quantified WT1 and RPS14 gene expression levels, in order to find their possible adjunctive value and their possible clinical impact. CC analysis showed 32% of patients with at least one aberration...
March 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28376560/hypoxia-mediated-epigenetic-regulation-of-stemness-in-brain-tumor-cells
#11
Authors Pankaj Prasad, Shivani Arora Mittal, Jonita Chongtham, Sujata Mohanty, Tapasya Srivastava
Activation of pluripotency regulatory circuit is an important event in solid tumor progression and the hypoxic microenvironment is known to enhance the stemness feature of some cells. This distinct population of cancer stem cells (CSCs)/tumor initiating cells (TICs) exist in a niche and augment invasion, metastasis and drug resistance. Previously, studies have reported global hypomethylation and site-specific aberrant methylation in gliomas along with other epigenetic modifications as important contributors to genomic instability during glioma progression...
April 4, 2017: Stem Cells
https://www.readbyqxmd.com/read/28370365/monocytosis-in-polycythemia-vera-clinical-and-molecular-correlates
#12
Daniela Barraco, Sonia Cerquozzi, Naseema Gangat, Mrinal M Patnaik, Terra Lasho, Christy Finke, Curtis A Hanson, Rhett P Ketterling, Animesh Pardanani, Ayalew Tefferi
Monocytosis (absolute monocyte count, AMC ≥1 x 10(9) /L) might accompany a spectrum of myeloid neoplasms, other than chronic myelomonocytic leukemia (CMML). In the current study, we examined the prevalence, laboratory and molecular correlates, and prognostic relevance of monocytosis in polycythemia vera (PV). Among 267 consecutive patients with World Health Organization (WHO)-defined PV, 55 (21%) patients displayed an AMC of ≥1 x 10(9) /L and 18 (7%) an AMC of ≥1.5 x 10(9) /L. In general, PV patients with monocytosis were significantly older and displayed higher frequencies of leukocytosis (81% vs 50% at AMC ≥1 x 10(9) /L) and TET2/SRSF2 mutations (57%/29% vs 19%/1% at AMC≥1...
March 28, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28350187/epigenetic-status-of-h19-igf2-imprinted-genes-and-loss-of-5-hydroxymethylcytosine-in-the-brain-of-cloned-goats
#13
Mingtian Deng, Caifang Ren, Zifei Liu, Guomin Zhang, Feng Wang, Yongjie Wan
In mammals, the imprinted genes play vital roles in development and are generally controlled by DNA methylation at imprinting control regions (ICRs). Recently, it was discovered that 5-hydroxymethylcytosine (5-hmC) is a stable epigenetic modification; however, its functions in cloned animal genomes have not yet been fully elucidated. In this study, we interrogated and quantified the 5-hmC levels in the brain of cloned goats and discovered upregulation of Uhrf1 (p < 0.001), Dnmt1 (p < 0.05), Dnmt3a (p < 0...
March 28, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28349832/differential-expression-of-ten-eleven-translocation-genes-in-endometrial-cancers
#14
Piotr Ciesielski, Paweł Jóźwiak, Katarzyna Wójcik-Krowiranda, Ewa Forma, Łukasz Cwonda, Sylwia Szczepaniec, Andrzej Bieńkiewicz, Magdalena Bryś, Anna Krześlak
Ten-eleven translocation proteins are α-ketoglutarate-dependent dioxygenases involved in the conversion of 5-methylcytosines (5-mC) to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine, and 5-carboxylcytosine that play a significant role in DNA demethylation. Deregulation of TET genes expression and changes in the level of 5-hmC are thought to be associated with the onset and progression of several types of cancer, but there are no such data related to endometrial cancer. The aim of the work was to investigate the messenger RNA expression levels of TET1, TET2, and TET3 in relation to clinicopathological characteristics of endometrial cancer as well as the correlation between expression of TET genes and the level of 5-hmC/5-mC...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28337768/tet2-mutations-in-b-cells-of-patients-affected-by-angioimmunoblastic-t-cell-lymphoma
#15
Friederike H Schwartz, Qian Cai, Eva Fellmann, Sylvia Hartmann, Mikko I Mäyränpää, Marja-Liisa Karjalainen-Lindsberg, Christer Sundström, René Scholtysik, Martin-Leo Hansmann, Ralf Küppers
Angioimmunoblastic T cell lymphomas (AITL) frequently carry mutations in the TET2 and IDH2 genes. TET2 mutations represent early genetic lesions as they were already detected in hematopoietic precursor cells of AITL patients. We show by analysis of whole tissue sections and microdissected PD1(+) cells that the frequency of TET2-mutated AITL is presumably even higher than reported (12/13 cases in our collection, 92%). In two thirds of informative AITL (6/9) also a fraction of B cells was TET2-mutated. Investigation of four AITL by TET2 and IGHV gene sequencing of single microdissected B cells showed that between 10-60% of polyclonal B cells in AITL lymph nodes harboured the identical TET2 mutations of the respective T cell lymphoma clone...
March 24, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28335073/clinical-characteristics-and-whole-exome-transcriptome-sequencing-of-coexisting-chronic-myeloid-leukemia-and-myelofibrosis
#16
Malathi Kandarpa, Yi-Mi Wu, Dan Robinson, Patrick William Burke, Arul M Chinnaiyan, Moshe Talpaz
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell (HSC) disorders that can be classified on the basis of genetic, clinical, phenotypic features. Genetic lesions such as JAK2 mutations and BCR-ABL translocation are often mutually exclusive in MPN patients and lead to essential thrombocythemia, polycythemia vera or myelofibrosis (ET/PV/MF) or chronic myeloid leukemia, respectively. Nevertheless, coexistence of these genetic aberrations in the same patient has been reported. Whether these aberrations occur in the same stem cell or a different cell is unclear, but an unstable genome in the HSCs seems to be the common antecedent...
March 23, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28331128/tet2-mutation-in-diffuse-large-b-cell-lymphoma
#17
Yoko Kubuki, Takumi Yamaji, Tomonori Hidaka, Takuro Kameda, Kotaro Shide, Masaaki Sekine, Ayako Kamiunten, Keiichi Akizuki, Haruko Shimoda, Yuuki Tahira, Kenichi Nakamura, Hiroo Abe, Tadashi Miike, Hisayoshi Iwakiri, Yoshihiro Tahara, Mitsue Sueta, Shojiro Yamamoto, Satoru Hasuike, Kenji Nagata, Akira Kitanaka, Kazuya Shimoda
Ten-eleven translocation-2 (TET2) mutation is frequently observed in myeloid malignancies, and loss-of-function of TET2 is essential for the initiation of malignant hematopoiesis. TET2 mutation presents across disease entities and was reported in lymphoid malignancies. We investigated TET2 mutations in 27 diffuse large B-cell lymphoma (DLBCL) patients and found a frameshift mutation in 1 case (3.7%). TET2 mutation occurred in some populations of DLBCL patients and was likely involved in the pathogenesis of their malignancies...
2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/28315400/multicolor-flow-cytometry-and-multigene-next-generation-sequencing-are-complementary-and-highly-predictive-for-relapse-in-acute-myeloid-leukemia-after-allogeneic-transplantation
#18
Bartlomiej M Getta, Sean M Devlin, Ross L Levine, Maria E Arcila, Abhinita S Mohanty, Ahmet Zehir, Martin S Tallman, Sergio A Giralt, Mikhail Roshal
Minimal residual disease (MRD) in acute myeloid leukemia (AML) is typically measured using multiparameter flow cytometry (MFC). Detection of leukemia mutations using multigene next-generation sequencing (NGS) can potentially be used to measure residual disease. We used a targeted 28-gene NGS panel to detect mutations and different-from-normal 10-color MFC to measure MRD in AML patients before allogeneic hematopoietic stem cell transplantation (HCT). Residual disease was defined when any abnormal blast population was detected using MFC and when any leukemia allele was detected with a variant allele frequency (VAF)  ≥ 5% using NGS...
March 15, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28314085/targeted-next-generation-sequencing-and-identification-of-risk-factors-in-world-health-organization-defined-atypical-chronic-myeloid-leukemia
#19
Mrinal M Patnaik, Daniela Barraco, Terra L Lasho, Christy M Finke, Kaaren Reichard, Katherine P Hoversten, Rhett P Ketterling, Naseema Gangat, Ayalew Tefferi
Atypical chronic myeloid leukemia (aCML) is an aggressive myeloid neoplasm with overlapping features of myelodysplastic syndromes (prominent granulocytic dysplasia) and myeloproliferative neoplasms (neutrophilic leukocytosis). We studied 25 molecularly-annotated and World Health Organization defined aCML patients; median age 70 years, 84% males. Cytogenetic abnormalities were seen in 36% and gene mutations in 100%. Mutational frequencies were, ASXL1 28%, TET2 16%, NRAS 16%, SETBP1 12%, RUNX1 12%, ETNK1 8% and PTPN11 4%...
March 17, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28298607/human-herpesvirus-6b-induces-hypomethylation-on-chromosome-17p13-3-correlating-with-increased-gene-expression-and-virus-integration
#20
Elin Engdahl, Nicky Dunn, Pitt Niehusmann, Sarah Wideman, Peter Wipfler, Albert J Becker, Tomas J Ekström, Malin Almgren, Anna Fogdell-Hahn
Human herpesvirus 6B (HHV-6B) is a neurotropic beta-herpesvirus that achieves latency by integrating its genome into host cell chromosomes. Several viruses can induce epigenetic modifications in their host cells, but no study has investigated the epigenetic modifications induced by HHV-6B. This study analyzed methylation with Illumina 450K array comparing HHV-6B infected and uninfected Molt-3 T cells three days post infection. Bisulfite pyrosequencing was used to validate Illumina results and investigate methylation over time in vitro Expression of genes was investigated using qPCR, and virus integration was investigated with PCR...
March 15, 2017: Journal of Virology
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