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https://www.readbyqxmd.com/read/29164635/influence-of-genetic-variants-of-idh1-idh2-tet2-and-dnmt3a-on-cytarabine-cytotoxicity-in-different-populations
#1
Y Wang, J K Lamba
WHAT IS KNOWN AND OBJECTIVE: Cytarabine (ara-C) is the mainstay of treatment for acute myeloid leukaemia. Resistance and toxicity are common reasons for its treatment failure. Genetic variants of susceptibility genes may be involved in resistance and toxicity to ara-C. This study is aimed to explore the association between influence of genetic variants of IDH1, IDH2, TET2 and DNMT3A on cytarabine cytotoxicity in European and/or African populations. METHODS: HapMap cell lines derived from European descent (CEU) and African descent (YRI) were exposed to ara-C at different concentrations (1, 5, 40 and 80 μmol/L)...
November 21, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29160764/dna-methylation-profile-in-chronic-myelomonocytic-leukemia-associates-with-distinct-clinical-biological-and-genetic-features
#2
Laura Palomo, Roberto Malinverni, Marta Cabezón, Blanca Xicoy, Montserrat Arnan, Rosa Coll, Helena Pomares, Olga García, Francisco Fuster-Tormo, Javier Grau, Evarist Feliu, Francesc Solé, Marcus Buschbeck, Lurdes Zamora
Chromosomal abnormalities are detected in 20-30% of patients with chronic myelomonocytic leukemia (CMML) and correlate with prognosis. On the mutation level, disruptive alterations are particularly frequent in chromatin regulatory genes. However, little is known about the consequential alterations in the epigenetic marking of the genome. Here, we report the analysis of genomic DNA methylation patterns of 64 CMML patients and 10 healthy controls, using a DNA methylation microarray focused on promoter regions...
November 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29150566/the-loss-of-tet2-promotes-cd8-t-cell-memory-differentiation
#3
Shannon A Carty, Mercy Gohil, Lauren B Banks, Renee M Cotton, Matthew E Johnson, Erietta Stelekati, Andrew D Wells, E John Wherry, Gary A Koretzky, Martha S Jordan
T cell differentiation requires appropriate regulation of DNA methylation. In this article, we demonstrate that the methylcytosine dioxygenase ten-eleven translocation (TET)2 regulates CD8(+) T cell differentiation. In a murine model of acute viral infection, TET2 loss promotes early acquisition of a memory CD8(+) T cell fate in a cell-intrinsic manner without disrupting Ag-driven cell expansion or effector function. Upon secondary recall, TET2-deficient memory CD8(+) T cells demonstrate superior pathogen control...
November 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29150453/high-bcat1-expression-mimics-idh-mutations-in-acute-myeloid-leukemia
#4
(no author information available yet)
High BCAT1 expression is linked to shorter survival in patients with IDH- and TET2-wild-type AML.
November 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29148541/integrated-genomic-analysis-identifies-deregulated-jak-stat-myc-biosynthesis-axis-in-aggressive-nk-cell-leukemia
#5
Liang Huang, Dan Liu, Na Wang, Shaoping Ling, Yuting Tang, Jun Wu, Lingtong Hao, Hui Luo, Xuelian Hu, Lingshuang Sheng, Lijun Zhu, Di Wang, Yi Luo, Zhen Shang, Min Xiao, Xia Mao, Kuangguo Zhou, Lihua Cao, Lili Dong, Xinchang Zheng, Pinpin Sui, Jianlin He, Shanlan Mo, Jin Yan, Qilin Ao, Lugui Qiu, Hongsheng Zhou, Qifa Liu, Hongyu Zhang, Jianyong Li, Jie Jin, Li Fu, Weili Zhao, Jieping Chen, Xin Du, Guoliang Qing, Hudan Liu, Xin Liu, Gang Huang, Ding Ma, Jianfeng Zhou, Qian-Fei Wang
Aggressive NK-cell leukemia (ANKL) is a rare form of NK cell neoplasm that is more prevalent among people from Asia and Central and South America. Patients usually die within days to months, even after receiving prompt therapeutic management. Here we performed the first comprehensive study of ANKL by integrating whole genome, transcriptome and targeted sequencing, cytokine array as well as functional assays. Mutations in the JAK-STAT pathway were identified in 48% (14/29) of ANKL patients, while the extracellular STAT3 stimulator IL10 was elevated by an average of 56-fold (P < 0...
November 17, 2017: Cell Research
https://www.readbyqxmd.com/read/29148089/impact-of-gene-mutations-on-treatment-response-and-prognosis-of-acute-myeloid-leukemia-secondary-to-myeloproliferative-neoplasms
#6
G Venton, F Courtier, A Charbonnier, E D'Incan, C Saillard, B Mohty, M J Mozziconacci, D Birnbaum, A Murati, N Vey, J Rey
Acute myeloid leukemias secondary (sAML) to myeloproliferative neoplasms (MPN) have variable clinical courses and outcomes, but remain almost always fatal. Large cohorts of sAML to MPN are difficult to obtain and there is very little scientific literature or prospective trials for determining robust prognostic markers and efficient treatments. We analyzed event-free survival (EFS) and overall survival (OS) of 73 patients with MPN who progressed to sAML, based on their epidemiological characteristics, the preexisting MPN, the different treatments received, the different prognostic groups and the responses achieved according to the ELN, and their mutational status determined by next-generation DNA sequencing (NGS)...
November 17, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29144447/bcat1-restricts-%C3%AE-kg-levels-in-aml-stem-cells-leading-to-idhmut-like-dna-hypermethylation
#7
Simon Raffel, Mattia Falcone, Niclas Kneisel, Jenny Hansson, Wei Wang, Christoph Lutz, Lars Bullinger, Gernot Poschet, Yannic Nonnenmacher, Andrea Barnert, Carsten Bahr, Petra Zeisberger, Adriana Przybylla, Markus Sohn, Martje Tönjes, Ayelet Erez, Lital Adler, Patrizia Jensen, Claudia Scholl, Stefan Fröhling, Sibylle Cocciardi, Patrick Wuchter, Christian Thiede, Anne Flörcken, Jörg Westermann, Gerhard Ehninger, Peter Lichter, Karsten Hiller, Rüdiger Hell, Carl Herrmann, Anthony D Ho, Jeroen Krijgsveld, Bernhard Radlwimmer, Andreas Trumpp
The branched-chain amino acid (BCAA) pathway and high levels of BCAA transaminase 1 (BCAT1) have recently been associated with aggressiveness in several cancer entities. However, the mechanistic role of BCAT1 in this process remains largely uncertain. Here, by performing high-resolution proteomic analysis of human acute myeloid leukaemia (AML) stem-cell and non-stem-cell populations, we find the BCAA pathway enriched and BCAT1 protein and transcripts overexpressed in leukaemia stem cells. We show that BCAT1, which transfers α-amino groups from BCAAs to α-ketoglutarate (αKG), is a critical regulator of intracellular αKG homeostasis...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29109788/decrease-in-lymphoid-specific-helicase-and-5-hydroxymethylcytosine-is-associated-with-metastasis-and-genome-instability
#8
Jiantao Jia, Ying Shi, Ling Chen, Weiwei Lai, Bin Yan, Yiqun Jiang, Desheng Xiao, Sichuan Xi, Ya Cao, Shuang Liu, Yan Cheng, Yongguang Tao
DNA methylation is an important epigenetic modification as a hallmark in cancer. Conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) by ten-eleven translocation (TET) family enzymes plays an important biological role in embryonic stem cells, development, aging and disease. Lymphoid specific helicase (LSH), a chromatin remodeling factor, is regarded as a reader of 5-hmC. Recent reports show that the level of 5-hmC is altered in various types of cancers. However, the change in 5-hmC levels in cancer and associated metastasis is not well defined...
2017: Theranostics
https://www.readbyqxmd.com/read/29108636/dynamic-expression-of-tet1-tet2-and-tet3-dioxygenases-in-mouse-and-human-placentas-throughout-gestation
#9
Joanna Rakoczy, Nisha Padmanabhan, Ada M Krzak, Jens Kieckbusch, Tereza Cindrova-Davies, Erica D Watson
INTRODUCTION: Throughout pregnancy, the placenta dynamically changes as trophoblast progenitors differentiate into mature trophoblast cell subtypes. This process is in part controlled by epigenetic regulation of DNA methylation leading to the inactivation of 'progenitor cell' genes and the activation of 'differentiation' genes. TET methylcytosine dioxygenases convert 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) during DNA demethylation events. Here, we determine the spatiotemporal expression of TET1, TET2, and TET3 in specific trophoblast cell populations of mouse and human placentas throughout gestation, and consider their role in trophoblast cell differentiation and function...
November 2017: Placenta
https://www.readbyqxmd.com/read/29108298/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...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29106571/retrieval-induced-upregulation-of-tet3-in-pyramidal-neurons-of-the-dorsal-hippocampus-mediates-cocaine-associated-memory-reconsolidation
#11
Cao Liu, Xue Sun, Zhilin Wang, Qiumin Le, Peipei Liu, Changyou Jiang, Feifei Wang, Lan Ma
Background: Memory retrieval refers to re-exposure to information previously encoded and stored in the brain. Following retrieval, a once-consolidated memory destabilizes and undergoes reconsolidation, during which gene expression changes to restabilize memory. Investigating epigenetic regulation during reconsolidation could provide insights into normal memory formation and pathological memory associated with psychiatric disorders. Methods: We used cocaine-induced conditioned place preference (CPP) to assess the cocaine-associated memory of mice and used chemogenetic methods to manipulate the activity of the pyramidal neurons in the dHC...
November 2, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29100007/vitamin-c-c-ing-a-new-way-to-fight-leukemia
#12
Katharina Schönberger, Nina Cabezas-Wallscheid
Metabolic cues and (epi-)genetic factors are emerging regulators of hematopoietic stem cell (HSC) potency. Two new studies in Nature and Cell, from Agathocleous et al. (2017) and Cimmino et al. (2017), respectively, show that vitamin C regulates HSC function and suppresses leukemogenesis by modulating Tet2 activity.
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29089070/-dna-hydroxymethylase-10-11-translocation-2-tet2-inhibits-mouse-macrophage-activation-and-polarization
#13
Bingyi Li, Yi Huo, Zhifeng Lin, Tao Wang
Objective To study the role of DNA hydroxymethylase 10-11 translocation 2 (TET2) in macrophage activation and polarization. Methods RAW264.7 macrophages were cultured in vitro and stimulated with 100 ng/mL LPS for 0, 1, 2, 4, 6 hours. Real-time quantitative PCR was used to detect TET2 mRNA expression. TET2 expression was knocked down with siRNA and the knock-down efficiency was evaluated by real-time quantitative PCR and Western blotting. Following siRNA transfection for 48 hours, RAW264.7 cells were stimulated by LPS for 4 hours, and then real-time quantitative PCR and ELISA were performed to detect the expressions of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and IL-12...
September 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/29069007/successful-eltrombopag-treatment-of-severe-refractory-thrombocytopenia-in-chronic-myelomonocytic-leukemia-two-cases-reports-a-care-compliant-article
#14
Yayue Gao, Ming Gong, Chunxia Zhang, Xudong Kong, Yigai Ma
RATIONALE: Thrombocytopenia in chronic myelomonocytic leukemia (CMML) is usually attributed to impaired marrow production resulting from cytotoxic drug use or CMML itself ("CMML-induced thrombocytopenia"). In very rare cases, immune thrombocytopenia (ITP) can be a complication of CMML ("CMML-associated ITP"). However, treatment of severe thrombocytopenia in patients with CMML is still a challenge. PATIENT CONCERNS: Case 1 was a 61-year-old female patient admitted to our hospital because of skin petechiae and purpura for 6 days...
October 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29052597/syk-expression-in-monomorphic-epitheliotropic-intestinal-t-cell-lymphoma
#15
Grit Mutzbauer, Katja Maurus, Clara Buszello, Jordan Pischimarov, Sabine Roth, Andreas Rosenwald, Andreas Chott, Eva Geissinger
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), formerly known as type II enteropathy associated T-cell lymphoma (type II EATL), is a rare, aggressive primary intestinal T-cell lymphoma with a poor prognosis and an incompletely understood pathogenesis. We collected 40 cases of MEITL and 27 cases of EATL, formerly known as type I EATL, and comparatively investigated the T-cell receptor (TCR) itself and associated signaling molecules using immunohistochemistry, amplicon deep sequencing and bisulfite pyrosequencing...
October 20, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29048538/improvement-of-foxp3-stability-through-cns2-demethylation-by-tet-enzyme-induction-and-activation
#16
Kazue Someya, Hiroko Nakatsukasa, Minako Ito, Taisuke Kondo, Kenn-Ichi Tateda, Takashi Akanuma, Ikuko Koya, Tsukasa Sanosaka, Jun Kohyama, Yu-Ichi Tsukada, Takeji Takamura-Enya, Akihiko Yoshimura
Since induced regulatory T cells (iTregs) can be produced in a large quantity in vitro, these cells are expected to be clinically useful to induce immunological tolerance in various immunological diseases. Foxp3 (Forkhead box P3) expression in iTregs is, however, unstable due to the lack of demethylation of the CpG island in the conserved non-coding sequence 2 (CNS2) of the Foxp3 locus. To facilitate the demethylation of CNS2, we over-expressed the catalytic domain (CD) of the ten-eleven translocation (TET) protein, which catalyzes the steps of the iterative demethylation of 5-methylcytosine...
August 1, 2017: International Immunology
https://www.readbyqxmd.com/read/29036962/-cladribine-in-the-treatment-of-tet2-refractory-acute-myeloid-leukemia-a-case-report
#17
J Liu, R Guo, Z X Jiang
No abstract text is available yet for this article.
October 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/29029424/microrna-22-can-regulate-expression-of-the-long-non-coding-rna-meg3-in-acute-myeloid-leukemia
#18
Hongxia Yao, Pei Sun, Mengling Duan, Lie Lin, Yanping Pan, Congming Wu, Xiangjun Fu, Hua Wang, Li Guo, Tianbo Jin, Yipeng Ding
AIM: Acute myeloid leukemia (AML) is the most common blood tumor with poor prognosis. At present, the research found that the pathogenesis of AML is related to many factors, such as recurrent somatic mutations and gene expression and epigenetic changes, however, the molecular mechanism of AML is still unclear. Long non-coding RNA MEG3 is a newly found tumor suppressor and plays a very important role in the regulation of a variety of tumor formation and progression. Studies found that the MEG3 expression was significantly decreased in AML...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29025587/addition-of-chromosomal-microarray-and-next-generation-sequencing-to-fish-and-classical-cytogenetics-enhances-genomic-profiling-of-myeloid-malignancies
#19
Sandeep Mukherjee, Malini Sathanoori, Zeq Ma, Matthew Andreatta, Patrick A Lennon, Scott R Wheeler, James L Prescott, Christopher Coldren, Terence Casey, Heather Rietz, Kristina Fasig, Randall Woodford, Taylor Hartley, David Spence, William Donnelan, Jesus Berdeja, Ian Flinn, Natalia Kozyr, Mark Bouzyk, Mick Correll, Hao Ho, Vladimir Kravtsov, Dana Tunnel, Pranil Chandra
Comprehensive genetic profiling is increasingly important for the clinical workup of hematologic tumors, as specific alterations are now linked to diagnostic characterization, prognostic stratification and therapy selection. To characterize relevant genetic and genomic alterations in myeloid malignancies maximally, we utilized a comprehensive strategy spanning fluorescence in situ hybridization (FISH), classical karyotyping, Chromosomal Microarray (CMA) for detection of copy number variants (CNVs) and Next generation Sequencing (NGS) analysis...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/28992762/mutations-in-tet2-and-dnmt3a-genes-are-associated-with-changes-in-global-and-gene-specific-methylation-in-acute-myeloid-leukemia
#20
Alberto Ponciano-Gómez, Adolfo Martínez-Tovar, Jorge Vela-Ojeda, Irma Olarte-Carrillo, Federico Centeno-Cruz, Efraín Garrido
Acute myeloid leukemia is characterized by its high biological and clinical heterogeneity, which represents an important barrier for a precise disease classification and accurate therapy. While epigenetic aberrations play a pivotal role in acute myeloid leukemia pathophysiology, molecular signatures such as change in the DNA methylation patterns and genetic mutations in enzymes needed to the methylation process can also be helpful for classifying acute myeloid leukemia. Our study aims to unveil the relevance of DNMT3A and TET2 genes in global and specific methylation patterns in acute myeloid leukemia...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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