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https://www.readbyqxmd.com/read/28107566/recent-advances-in-understanding-clonal-haematopoiesis-in-aplastic-anaemia
#1
REVIEW
Natasha Stanley, Timothy S Olson, Daria V Babushok
Acquired aplastic anaemia (AA) is an immune-mediated bone marrow failure disorder inextricably linked to clonal haematopoiesis. The majority of AA patients have somatic mutations and/or structural chromosomal abnormalities detected as early as at diagnosis. In contrast to other conditions linked to clonal haematopoiesis, the clonal signature of AA reflects its immune pathophysiology. The most common alterations are clonal expansions of cells lacking glycophosphotidylinositol-anchored proteins, loss of human leucocyte antigen alleles, and mutations in BCOR/BCORL1, ASXL1 and DNMT3A...
January 20, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28104825/effect-of-bovine-oviductal-extracellular-vesicles-on-embryo-development-and-quality-in-vitro
#2
Ricaurte Lopera-Vasquez, Meriem Hamdi, Veronica Maillo, Alfonso Gutierrez-Adan, Pablo Bermejo-Alvarez, Miguel Angel Ramirez, Maria Yañez-Mo, Dimitrios Rizos
The aim of this study was to evaluate the effect of extracellular vesicles (EV) from oviductal fluid (OF), either from the ampulla or isthmus, on the development and quality of in vitro cultured bovine embryos. Zygotes were cultured in synthetic oviduct fluid (SOF+3mg/ml BSA) without calf serum (C- group), in the presence of 3x105 EV/ml from ampullary or isthmic OF at either 1x104xg (10k) and 1x105xg (100k), and compared with SOF+5% FCS (C+ group). OF-EV size and concentration were assessed by electron microscopy and nanotracking analysis system...
January 19, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28102729/chronic-myelomonocytic-leukemia-with-double-mutations-in-dnmt3a-and-flt3-itd-treated-with-decitabine-and-sorafenib
#3
Jia Gu, Zhiqiong Wang, Min Xiao, Xia Mao, Li Zhu, Ying Wang, Wei Huang
Chronic myelomonocytic leukemia (CMML) is a heterogeneous neoplastic hematologic disorder with worse overall survival. Half of CMML have mutations, but case with concomitant mutations of DNA methyltransferase 3A (DNMT3A) and Internal tandem duplications of the juxtamembrane domain of FLT3 (FLT3-ITD) in CMML was not reported before. We reported a 51-year-old man who had CMML with concomitant mutations in DNMT3A and FLT3-ITD.The patient received decitabine and sorafenib combined treatment. In this report, we reviewed DNMT3A mutation and FLT3 mutation, and we reviewed treatment of decitabine and sorafenib...
January 19, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28100593/clinical-implications-of-dnmt3a-mutations-in-a-southeast-asian-cohort-of-acute-myeloid-leukaemia-patients
#4
Marcus Tan, Isaac K S Ng, Zhaojin Chen, Kenneth Ban, Christopher Ng, Lily Chiu, Elaine Seah, Mingxuan Lin, Bee Choo Tai, Benedict Yan, Chin Hin Ng, Wee-Joo Chng
AIMS: In recent years, genomic technologies have enabled the identification of mutations in acute myeloid leukaemia (AML). DNMT3A is a recurrently mutated epigenetic modifier gene in AML. To date, the prognostic significance of DNMT3A mutations has not been studied in a Southeast Asian AML population. We sought to investigate the clinical implications of DNMT3A mutations in a Southeast Asian cohort of AML patients. METHODS: DNMT3A mutations were identified using a targeted next-generation sequencing panel in 157 AML patients...
January 18, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28098901/effect-of-evodiamine-and-berberine-on-the-interaction-between-dnmts-and-target-micrornas-during-malignant-transformation-of-the-colon-by-tgf-%C3%AE-1
#5
Chao Huang, Hong Liu, Xiu-Li Gong, Li-Yun Wu, Bin Wen
The tissue microenvironment functions as a crucial player in carcinogenesis, and transforming growth factor-β1 (TGF-β1) within the microenvironment stimulates the formation of neoplasms. Using an in vitro model of malignancy induced by TGF-β1, we assessed the effect of evodiamine and berberine on the interaction between DNA methyltransferases (DNMTs) and target microRNAs (miRNAs) in the model. Colon tissues from neonatal rats 7 days of age were cultured and malignancy was induced by TGF-β1 in vitro for 48 h, and then the tissues were respectively treated with evodiamine and berberine for 24 h...
January 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28074931/eid3-directly-associates-with-dnmt3a-during-transdifferentiation-of-human-umbilical-cord-mesenchymal-stem-cells-to-npc-like-cells
#6
Liang Luo, Wen-Jin Chen, James Q Yin, Ru-Xiang Xu
There has been recently been increased interest in the plasticity of human umbilical cord mesenchymal stem cells (UMSCs) and their potential in the treatment of neurological disorders. In this study, UMSCs were transdifferentiated into neural stem-like cells (uNSCL), these cells grow in neurosphere-like structures and express high levels of NSCs markers. Epigenetics-related gene screening was here used to assess the relationship between E1A-like inhibitor of differentiation 3 (EID3), a p300 inhibitor, and DNA methyltransferase 3 A (DNMT3A) during the transdifferentiation of UMSCs into uNSCL in vitro...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28070990/a-targeted-next-generation-sequencing-in-the-molecular-risk-stratification-of-adult-acute-myeloid-leukemia-implications-for-clinical-practice
#7
Po-Han Lin, Huei-Ying Li, Sheng-Chih Fan, Tzu-Hang Yuan, Ming Chen, Yu-Hua Hsu, Yu-Hsuan Yang, Long-Yuan Li, Su-Peng Yeh, Li-Yuan Bai, Yu-Min Liao, Chen-Yuan Lin, Ching-Yun Hsieh, Ching-Chan Lin, Che-Hung Lin, Ming-Yu Lien, Tzu-Ting Chen, Yen-Hsuan Ni, Chang-Fang Chiu
Conventional cytogenetics can categorize patients with acute myeloid leukemia (AML) into favorable, intermediate, and unfavorable-risk groups; however, patients with intermediate-risk cytogenetics represent the major population with variable outcomes. Because molecular profiling can assist with AML prognosis and next-generation sequencing allows simultaneous sequencing of many target genes, we analyzed 260 genes in 112 patients with de novo AML who received standard treatment. Multivariate analysis showed that karyotypes and mutation status of TET2, PHF6, KIT, and NPM1(mutation) /FLT3- internal tandem duplication (ITD)(negative) were independent prognostic factors for the entire cohort...
January 10, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28069796/high-dietary-folate-in-pregnant-mice-leads-to-pseudo-mthfr-deficiency-and-altered-methyl-metabolism-with-embryonic-growth-delay-and-short-term-memory-impairment-in-offspring
#8
Renata H Bahous, Nafisa M Jadavji, Liyuan Deng, Marta Cosín-Tomás, Jessica Lu, Olga Malysheva, Kit-Yi Leung, Ming-Kai Ho, Mercè Pallàs, Perla Kaliman, Nicholas DE Greene, Barry J Bedell, Marie A Caudill, Rima Rozen
Methylenetetrahydrofolate reductase (MTHFR) generates methyltetrahydrofolate for methylation reactions. Severe MTHFR deficiency results in homocystinuria and neurologic impairment. Mild MTHFR deficiency (677C>T polymorphism) increases risk for complex traits, including neuropsychiatric disorders. Although low dietary folate impacts brain development, recent concerns have focused on high folate intake following food fortification and increased vitamin use. Our goal was to determine whether high dietary folate during pregnancy affects brain development in murine offspring...
January 9, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28061354/dominating-the-negative-how-dnmt3a-mutations-contribute-to-aml-pathogenesis
#9
Grant A Challen
Somatic mutations in DNMT3A are one of the most prevalent genetic abnormalities found in acute myeloid leukemia (AML) patients. A new study by Guryanova et al. sheds mechanistic insight into how the most common DNMT3A variant protein contributes to AML using a combination of mouse genetics and primary patient samples.
January 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28058491/evaluating-the-impact-of-genetic-and-epigenetic-aberrations-on-survival-and-response-in-acute-myeloid-leukemia-patients-receiving-epigenetic-therapy
#10
Jan K Hiller, Claudia Schmoor, Verena I Gaidzik, Charlotte Schmidt-Salzmann, Arzu Yalcin, Mahmoud Abdelkarim, Nadja Blagitko-Dorfs, Konstanze Döhner, Lars Bullinger, Justus Duyster, Michael Lübbert, Björn Hackanson
Treatment with hypomethylating agents such as decitabine, which results in overall response rates of up to 50%, has become standard of care in older patients with acute myeloid leukemia (AML) who are not candidates for intensive chemotherapy. However, there still exists a lack of prognostic and predictive molecular biomarkers that enable selection of patients who are likely to benefit from epigenetic therapy. Here, we investigated distinct genetic (FLT3-ITD, NPM1, DNMT3A) and epigenetic (estrogen receptor alpha (ERα), C/EBPα, and OLIG2) aberrations in 87 AML patients from the recently published phase II decitabine trial (AML00331) to identify potential biomarkers for patients receiving hypomethylating therapy...
January 5, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28058097/genetics-and-epigenetics-of-myelodysplastic-syndromes-and-response-to-drug-therapy-new-insights
#11
REVIEW
Saeid Shahrabi, Abbas Khosravi, Mohammad Shahjahani, Fakher Rahim, Najmaldin Saki
Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic neoplasms ocurring mostly in the elderly. The clinical outcome of MDS patients is still poor despite progress in treatment approaches. About 90% of patients harbor at least one somatic mutation. This review aimed to assess the potential of molecular abnormalities in understanding pathogenesis, prognosis, diagnosis and in guiding choice of proper therapy in MDS patients. Papers related to this topic from 2000 to 2016 in PubMed and Scopus databases were searched and studied...
October 10, 2016: Oncology Reviews
https://www.readbyqxmd.com/read/28055238/valproic-acid-increases-histone-acetylation-and-alters-gene-expression-in-the-donor-cells-but-does-not-improve-the-in-vitro-developmental-competence-of-buffalo-bubalus-bubalis-embryos-produced-by-hand-made-cloning
#12
Naresh L Selokar, Monika Saini, Himanshu Agrawal, Prabhat Palta, Manmohan Singh Chauhan, Radheysham Manik, Suresh Kumar Singla
Use of histone deacetylase inhibitors (HDACis) is believed to improve the developmental competence and quality of cloned embryos produced. We examined the effects of treatment of buffalo fibroblasts with valproic acid (VPA), a HDACi on these cells and on embryos produced from them by hand-made cloning. VPA treatment (1.5, 3.0, or 4.5 mM) altered (p < 0.05) the growth characteristics and relative expression level of HDAC1, DNMT1, DNMT3a, P53, and CASPASE3, and the global level of H3K9/14ac, H4K5ac, and H3K18ac but not H3K27me3 in the cells...
January 5, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28052028/establishment-and-characterization-of-hypomethylating-agent-resistant-cell-lines-molm-aza-1-and-molm-dec-5
#13
Eun-Hye Hur, Seung-Hyun Jung, Bon-Kwan Goo, Juhyun Moon, Yunsuk Choi, Dae Ro Choi, Yeun-Jun Chung, Je-Hwan Lee
Two hypomethylating agents (HMAs), azacitidine and decitabine, have demonstrated clinical activities in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML); however, potential problems include development of acquired resistance. HMA-resistant patients have very poor prognosis and this cohort of patients constitutes an important area of research. To understand the mechanisms underlying HMA-resistance and to overcome it, we established an azacitidine-resistant cell line, MOLM/AZA-1 and a decitabine-resistant cell line, MOLM/DEC-5 using MOLM-13...
December 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/28049695/dysregulated-dna-methyltransferase-3a-upregulates-igfbp5-to-suppress-trophoblast-cell-migration-and-invasion-in-preeclampsia
#14
Yuanhui Jia, Ting Li, Xiaojie Huang, Xianghong Xu, Xinyao Zhou, Linyan Jia, Jingping Zhu, Dandan Xie, Kai Wang, Qian Zhou, Liping Jin, Jiqin Zhang, Tao Duan
Preeclampsia is a unique multiple system disorder during human pregnancy, which affects ≈5% to 8% of pregnancies. Its risks and complications have become the major causes of maternal and fetal morbidity and mortality. Although abnormal placentation to which DNA methylation dysregulation is always linked is speculated to be one of the reasons causing preeclampsia, the underlying mechanisms still remain elusive to date. Here we revealed that aberrant DNA methyltransferase 3A (DNMT3A) plays a critical role in preeclampsia...
January 3, 2017: Hypertension
https://www.readbyqxmd.com/read/28043331/avermectin-induced-global-dna-hypomethylation-and-over-expression-of-heat-shock-proteins-in-cardiac-tissues-of-pigeon
#15
Ci Liu, Ye Cao, Shuo Zhou, Pervez Ahmed Khoso, Shu Li
Despite increasing evidences pointing to residues of avermectin (AVM) pose toxic effects on non-target organisms in environment, but the data in pigeon is insufficient. The alteration of global DNA methylation and response of heat shock proteins (Hsps) are important for assessing the AVM toxicity in cardiac tissues of pigeon (Columba livia). To investigate the effects of AVM exposure in cardiac tissues of pigeon, we detected the expression levels of DNA methyltransferases (Dnmts), methylated DNA-binding domain protein 2 (MBD2), and Hsp 60, 70 and 90...
January 2017: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/28028029/genetic-basis-and-molecular-pathophysiology-of-classical-myeloproliferative-neoplasms
#16
William Vainchenker, Robert Kralovics
The genetic landscape of classical myeloproliferative neoplasm (MPN) is in large part elucidated. The MPN restricted driver mutations including those in JAK2, calreticulin (CALR) and MPL abnormally activate the cytokine receptor/JAK2 pathway and their downstream effectors, more particularly the STATs. The most frequent mutation, JAK2V617F, activates the three main myeloid cytokine receptors (EPOR, G-CSFR and MPL) whereas CALR or MPL mutants are restricted to MPL activation. This explains why JAK2V617F is associated with polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) whereas CALR and MPL mutants are found in ET and PMF...
December 27, 2016: Blood
https://www.readbyqxmd.com/read/28017968/mutations-in-notch1-pest-domain-orchestrate-ccl19-driven-homing-of-chronic-lymphocytic-leukemia-cells-by-modulating-the-tumor-suppressor-gene-dusp22
#17
F Arruga, B Gizdic, C Bologna, S Cignetto, R Buonincontri, S Serra, T Vaisitti, K Gizzi, N Vitale, G Garaffo, E Mereu, F Diop, F Neri, D Incarnato, M Coscia, J Allan, R Piva, S Oliviero, R R Furman, D Rossi, G Gaidano, S Deaglio
Even if NOTCH1 is commonly mutated in Chronic Lymphocytic Leukemia (CLL), its functional impact in the disease remains unclear. Using CRISPR/Cas9-generated Mec-1 cell line models, we show that NOTCH1 regulates growth and homing of CLL cells by dictating expression levels of the tumor suppressor gene DUSP22. Specifically, NOTCH1 affects the methylation of DUSP22 promoter by modulating a nuclear complex, which tunes the activity of DNA methyltransferase 3A (DNMT3A). These effects are enhanced by PEST-domain mutations, which stabilize the molecule and prolong signaling...
December 26, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28017732/photoperiodic-and-ovarian-steroid-regulation-of-histone-deacetylase-1-2-and-3-in-siberian-hamster-phodopus-sungorus-reproductive-tissues
#18
Eloise W J Lynch, Christopher S Coyle, Tyler J Stevenson
Epigenetic modifications in reproductive tissues have predominantly focused on pathological conditions, such as ovarian and uterine cancers. The contribution of DNA methylation and histone acetylation to the timing and control of fertility is not well described. Siberian hamsters provide an important model to investigate the relatively short-term regulation of fertility (e.g. estrous) as well as long-term timing of breeding (e.g. seasonal). Recent work has shown that DNA methyltransferase 3a (dnmt3a) expression is associated with reproductive involution...
December 22, 2016: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28007692/micrornas-are-stored-in-human-mii-oocyte-and-their-expression-profile-changes-in-reproductive-aging
#19
Rosalia Battaglia, Maria Elena Vento, Marco Ragusa, Davide Barbagallo, Alessandro La Ferlita, Giovanna Di Emidio, Placido Borzí, Paolo Giovanni Artini, Paolo Scollo, Carla Tatone, Michele Purrello, Cinzia Di Pietro
Maternal RNAs are synthesized by the oocyte during its growth; some of them are utilized for oocyte-specific processes and metabolism, others are stored and used during early development before embryonic genome activation. The appropriate expression of complex sets of genes is needed for oocyte maturation and early embryo development. In spite of the basic role of noncoding RNAs in the regulation of gene expression, few studies have analyzed their role in human oocytes. In this study, we identified the microRNAs (miRNAs) expressed in human metaphase II stage oocytes, and found that some of them are able to control pluripotency, chromatin remodeling, and early embryo development...
December 2016: Biology of Reproduction
https://www.readbyqxmd.com/read/28003281/dnmt3a-in-leukemia
#20
Lorenzo Brunetti, Michael C Gundry, Margaret A Goodell
DNA methylation is an epigenetic process involved in development, aging, and cancer. Although the advent of new molecular techniques has enhanced our knowledge of how DNA methylation alters chromatin and subsequently affects gene expression, a direct link between epigenetic marks and tumorigenesis has not been established. DNMT3A is a de novo DNA methyltransferase that has recently gained relevance because of its frequent mutation in a large variety of immature and mature hematologic neoplasms. DNMT3A mutations are early events during cancer development and seem to confer poor prognosis to acute myeloid leukemia (AML) patients making this gene an attractive target for new therapies...
December 21, 2016: Cold Spring Harbor Perspectives in Medicine
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