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https://www.readbyqxmd.com/read/28937943/multiomics-analysis-of-tumor-microenvironment-reveals-gata2-and-mirna-124-3p-as-potential-novel-biomarkers-in-ovarian-cancer
#1
Esra Gov, Medi Kori, Kazim Yalcin Arga
Ovarian cancer is a common and, yet, one of the most deadly human cancers due to its insidious onset and the current lack of robust early diagnostic tests. Tumors are complex tissues comprised of not only malignant cells but also genetically stable stromal cells. Understanding the molecular mechanisms behind epithelial-stromal crosstalk in ovarian cancer is a great challenge in particular. In the present study, we performed comparative analyses of transcriptome data from laser microdissected epithelial, stromal, and ovarian tumor tissues, and identified common and tissue-specific reporter biomolecules-genes, receptors, membrane proteins, transcription factors (TFs), microRNAs (miRNAs), and metabolites-by integration of transcriptome data with genome-scale biomolecular networks...
September 22, 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28930689/integrating-enhancer-mechanisms-to-establish-a-hierarchical-blood-development-program
#2
Charu Mehta, Kirby D Johnson, Xin Gao, Irene M Ong, Koichi R Katsumura, Skye C McIver, Erik A Ranheim, Emery H Bresnick
Hematopoietic development requires the transcription factor GATA-2, and GATA-2 mutations cause diverse pathologies, including leukemia. GATA-2-regulated enhancers increase Gata2 expression in hematopoietic stem/progenitor cells and control hematopoiesis. The +9.5-kb enhancer activates transcription in endothelium and hematopoietic stem cells (HSCs), and its deletion abrogates HSC generation. The -77-kb enhancer activates transcription in myeloid progenitors, and its deletion impairs differentiation. Since +9...
September 19, 2017: Cell Reports
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
#3
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/28903318/myc-dependent-recruitment-of-runx1-and-gata2-on-the-set-oncogene-promoter-enhances-pp2a-inactivation-in-acute-myeloid-leukemia
#4
Raffaella Pippa, Ana Dominguez, Raquel Malumbres, Akinori Endo, Elena Arriazu, Nerea Marcotegui, Elizabeth Guruceaga, María D Odero
The SET (I2PP2A) oncoprotein is a potent inhibitor of protein phosphatase 2A (PP2A) that regulates many cell processes and important signaling pathways. Despite the importance of SET overexpression and its prognostic impact in both hematologic and solid tumors, little is known about the mechanisms involved in its transcriptional regulation. In this report, we define the minimal promoter region of the SET gene, and identify a novel multi-protein transcription complex, composed of MYC, SP1, RUNX1 and GATA2, which activates SET expression in AML...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28887433/the-neurobeachin-like-2-protein-regulates-mast-cell-homeostasis
#5
Sebastian Drube, Randy Grimlowski, Carsten Deppermann, Julia Fröbel, Florian Kraft, Nico Andreas, David Stegner, Jan Dudeck, Franziska Weber, Mandy Rödiger, Christiane Göpfert, Julia Drube, Daniela Reich, Bernhard Nieswandt, Anne Dudeck, Thomas Kamradt
The neurobeachin-like 2 protein (Nbeal2) belongs to the family of beige and Chediak-Higashi (BEACH) domain proteins. Loss-of-function mutations in the human NBEAL2 gene or Nbeal2 deficiency in mice cause gray platelet syndrome, a bleeding disorder characterized by macrothrombocytopenia, splenomegaly, and paucity of α-granules in megakaryocytes and platelets. We found that in mast cells, Nbeal2 regulates the activation of the Shp1-STAT5 signaling axis and the composition of the c-Kit/STAT signalosome. Furthermore, Nbeal2 mediates granule formation and restricts the expression of the transcription factors, IRF8, GATA2, and MITF as well as of the cell-cycle inhibitor p27, which are essential for mast cell differentiation, proliferation, and cytokine production...
September 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28866324/effects-of-in-vivo-deletion-of-gata2-in-bone-marrow-stromal-cells
#6
Shin Hasegawa, Tohru Fujiwara, Yoko Okitsu, Hiroki Kato, Yuki Sato, Noriko Fukuhara, Yasushi Onishi, Ritsuko Shimizu, Masayuki Yamamoto, Hideo Harigae
The bone marrow (BM) microenvironment comprises multiple stem cell niches derived from BM mesenchymal stem cells (BM-MSCs). Previous in vitro analyses have suggested that transcription factor GATA2 plays an important role in adipocyte differentiation of BM-mesenchymal stem cells as well as in hematopoietic support, but the role of GATA2 in vivo remains unknown. We evaluated GATA2 effects in BM-MSC in vivo. Expression profiling analysis of Gata2 knockout Ter119(-)CD45(-) mesenchymal stromal cells obtained from compact bone from tamoxifen-treated Gata2 conditional knockout mice (Gata2(f/f)/ER-Cre mice) revealed upregulation of 110 genes and downregulation of 141 by a factor of 2...
August 30, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28830460/gene-mutational-pattern-and-expression-level-in-560-acute-myeloid-leukemia-patients-and-their-clinical-relevance
#7
Yong-Mei Zhu, Pan-Pan Wang, Jin-Yan Huang, Yun-Shuo Chen, Bing Chen, Yu-Jun Dai, Han Yan, Yi Hu, Wen-Yan Cheng, Ting-Ting Ma, Sai-Juan Chen, Yang Shen
BACKGROUND: Cytogenetic aberrations and gene mutations have long been regarded as independent prognostic markers in AML, both of which can lead to misexpression of some key genes related to hematopoiesis. It is believed that the expression level of the key genes is associated with the treatment outcome of AML. METHODS: In this study, we analyzed the clinical features and molecular aberrations of 560 newly diagnosed non-M3 AML patients, including mutational status of CEBPA, NPM1, FLT3, C-KIT, NRAS, WT1, DNMT3A, MLL-PTD and IDH1/2, as well as expression levels of MECOM, ERG, GATA2, WT1, BAALC, MEIS1 and SPI1...
August 22, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28825694/monozygotic-twins-with-gata2-deficiency-same-haploidentical-related-donor-different-severity-of-gvhd
#8
N N Shah, M Parta, K Baird, H Rafei, K Cole, S M Holland, D D Hickstein
No abstract text is available yet for this article.
August 21, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28814615/single-cell-gene-expression-of-the-bovine-blastocyst
#9
Veronica M Negrón-Pérez, Yanping Zhang, Peter J Hansen
The first two differentiation events in the blastocyst result in three cell types - epiblast, trophectoderm (TE), and hypoblast. The purpose here was to identify molecular markers for each cell type in the bovine and evaluate differences in gene expression among individual cells of each lineage. The cDNA from 67 individual cells from dissociated blastocysts was used to determine transcript abundance for 96 genes implicated as cell lineage markers in other species or potentially involved in developmental processes...
August 16, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28807932/reducing-inflammatory-cytokine-production-from-renal-collecting-duct-cells-by-inhibiting-gata2-ameliorates-acute-kidney-injury
#10
Lei Yu, Takashi Moriguchi, Hiroshi Kaneko, Makiko Hayashi, Atsushi Hasegawa, Masahiro Nezu, Hideyuki Saya, Masayuki Yamamoto, Ritsuko Shimizu
Acute kidney injury (AKI) is a leading cause of chronic kidney disease. Proximal tubules are considered to be the primary origin of pathogenic inflammatory cytokines in AKI. However, it remains unclear whether other cell types, including collecting duct (CD) cells, participate in inflammatory processes. The transcription factor GATA2 is specifically expressed in CD cells and maintains their cellular identity. To explore the pathophysiological function of GATA2 in AKI, we generated renal tubular cell-specific Gata2 deletion (G2CKO) mice and examined their susceptibility to ischemia-reperfusion injury (IRI)...
August 14, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28801348/incidental-detection-of-germline-variants-of-potential-clinical-significance-by-massively-parallel-sequencing-in-haematological-malignancies
#11
Costas K Yannakou, Kate Jones, Georgina L Ryland, Ella R Thompson, Gareth Reid, Michelle McBean, Alison Trainer, David Westerman, Piers Blombery
Massively parallel sequencing (MPS) technology has become routinely available for diagnosis, prognostication and therapeutic decision-making in haematological malignancies. However, increased throughput and wider coverage of genes can have unintended consequences. Germline variants of potential clinical significance (GVPCSs) detected during cancer testing may have implications for patients and families beyond the biological evaluation of a specific tumour. 721 reports generated from MPS panels used in the routine testing of myeloid and lymphoid malignancies were reviewed and variants within genes of potential germline relevance (TP53, RUNX1, GATA2 and WT1 in all contexts and CBL, KRAS and NRAS in the setting of juvenile myelomonocytic leukaemia) were analysed...
August 11, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28760552/cdkn2b-as-may-indirectly-regulate-coronary-artery-disease-associated-genes-via-targeting-mir-92a
#12
Ming Cheng, Shoukuan An, Junquan Li
OBJECTIVE: Coronary artery disease (CAD) has a high mortality rate and consists of multiple condition, including stable/unstable angina, sudden cardiac death, and myocardial infarction. This study is aimed to explore the pathogenesis of CAD. METHODS: Datasets of GSE20680 (including 87 CAD samples and 52 normal samples) and GSE20681 (including 99 CAD samples and 99 normal samples) were obtained from Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified by MetaDE...
September 20, 2017: Gene
https://www.readbyqxmd.com/read/28752392/gata2-gene-analysis-in-several-forms-of-hematological-malignancies-including-familial-aggregations
#13
Walid Sabri Hamadou, Rahma Mani, Sawsen Besbes, Violaine Bourdon, Yosra Ben Youssef, François Eisinger, Véronique Mari, Paul Gesta, Hélène Dreyfus, Valérie Bonadona, Catherine Dugast, Hélène Zattara, Laurence Faivre, Testsuro Noguchi, Abderrahim Khélif, Hagay Sobol, Zohra Soua
The genetic predisposition to familial hematological malignancies has been previously reported highlighting inherited gene mutations. Several genes have been reported but genetic basis remains not well defined. In this study, we extended our investigation to a potential candidate GATA2 gene which was analyzed by direct sequencing in 119 cases including familial aggregations with a variety of hematological malignancies and sporadic acute leukemia belonging to Tunisian and French populations. We reported a deleterious p...
July 27, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28747912/acquired-senescent-t-cell-phenotype-correlates-with-clinical-severity-in-gata-binding-protein-2-deficient-patients
#14
Raquel Ruiz-García, Carmen Rodríguez-Vigil, Francisco Manuel Marco, Fernando Gallego-Bustos, María José Castro-Panete, Laura Diez-Alonso, Carlos Muñoz-Ruiz, Jesús Ruiz-Contreras, Estela Paz-Artal, Luis Ignacio González-Granado, Luis Miguel Allende
GATA binding protein 2 (GATA2) deficiency is a rare disorder of hematopoiesis, lymphatics, and immunity caused by spontaneous or autosomal dominant mutations in the GATA2 gene. Clinical manifestations range from neutropenia, lymphedema, deafness, to severe viral and mycobacterial infections, bone marrow failure, and acute myeloid leukemia. Patients also present with monocytopenia, dendritic cell, B- and natural killer (NK)-cell deficiency. We studied the T-cell and NK-cell compartments of four GATA2-deficient patients to assess if changes in these lymphocyte populations could be correlated with clinical phenotype...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28688371/6-2-fluorotelomer-carboxylic-acid-6-2-ftca-exposure-induces-developmental-toxicity-and-inhibits-the-formation-of-erythrocytes-during-zebrafish-embryogenesis
#15
Guohui Shi, Qianqian Cui, Yitao Pan, Nan Sheng, Yong Guo, Jiayin Dai
Saturated fluorotelomer carboxylic acids (FTCAs) are intermediates in the degradation of fluorotelomer alcohols (FTOHs) to perfluorinated carboxylic acids (PFCAs). Recent studies have detected FTCAs in precipitation, surface waters, and wildlife, but few studies have focused on their toxicity. In this study, zebrafish embryos were exposed to different concentrations of 6:2 FTCA (0, 4, 8, and 12mg/L) from 6 to 120h post-fertilization (hpf) to investigate its developmental toxicity. Results showed that 6:2 FTCA exposure decreased the hatching and survival percentages, reduced the heart rate, and increased the malformation of zebrafish embryos...
September 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28680581/endothelial-follistatin-like-1-regulates-the-postnatal-development-of-the-pulmonary-vasculature-by-modulating-bmp-smad-signaling
#16
Navessa P Tania, Harm Maarsingh, I Sophie T Bos, Andrea Mattiotti, Stuti Prakash, Wim Timens, Quinn D Gunst, Luis J Jimenez-Borreguero, Martina Schmidt, Maurice J B van den Hoff, Reinoud Gosens
Bone morphogenetic protein (BMP) signaling regulates vascular smooth muscle maturation, endothelial cell proliferation, and tube formation. The endogenous BMP antagonist Follistatin-like 1 (Fstl1) is highly expressed in pulmonary vascular endothelium of the developing mouse lung, suggesting a role in pulmonary vascular formation and vascular homeostasis. The aim of this study was to investigate the role of Fstl1 in the pulmonary vascular endothelium. To this aim, Fstl1 was conditionally deleted from endothelial and endothelial-derived cells using Tie2-cre driven Fstl1-KO mice (Fstl1-eKO mice)...
March 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28675510/the-co-regulatory-networks-of-tumor-suppressor-genes-oncogenes-and-mirnas-in-colorectal-cancer
#17
Martha L Slattery, Jennifer S Herrick, Lila E Mullany, Wade S Samowitz, John R Sevens, Lori Sakoda, Roger K Wolff
Tumor suppressor genes (TSGs) and oncogenes (OG) are involved in carcinogenesis. MiRNAs also contribute to cellular pathways leading to cancer. We use data from 217 colorectal cancer (CRC) cases to evaluate differences in TSGs and OGs expression between paired CRC and normal mucosa and evaluate how TSGs and OGs are associated with miRNAs. Gene expression data from RNA-Seq and miRNA expression data from Agilent Human miRNA Microarray V19.0 were used. We focus on genes most strongly associated with CRC (fold change (FC) of ≥1...
November 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28655875/proximal-gata-binding-sites-are-essential-for-human-hsd3b1-gene-transcription-in-the-placenta
#18
Tsai-Chun Lai, Hsiao-Fang Li, Yu-Shian Li, Pei-Yu Hung, Ming-Kwang Shyu, Meng-Chun Hu
The enzyme 3β-hydroxysteroid dehydrogenase/isomerase (3β-HSD) is involved in the synthesis of active steroid hormones. Two human 3β-HSD isoforms are expressed in a tissue-specific pattern. HSD3B1 (type I) expression is essential to produce progesterone for pregnancy maintenance. To understand the mechanisms of human HSD3B1 activation in the placenta, 2.2 kb of 5'-flanking sequence and 5'-deletions were fused to the luciferase reporter gene and transfected into human JEG-3 cells. The proximal -238/+337 sequence had the highest promoter activity...
June 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28643018/heterogeneity-of-gata2-related-myeloid-neoplasms
#19
REVIEW
Shinsuke Hirabayashi, Marcin W Wlodarski, Emilia Kozyra, Charlotte M Niemeyer
The GATA2 gene codes for a master hematopoietic transcription factor that is essential for the proliferation and maintenance of hematopoietic stem and progenitor cells. Heterozygous germline mutations in GATA2 have been initially associated with several clinical entities that are now collectively defined as GATA2 deficiency. Despite pleiotropic clinical manifestations, the high propensity for the development of myelodysplastic syndromes (MDS) constitutes the most common clinical denominator of this major MDS predisposition syndrome...
August 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28642594/differential-effects-on-gene-transcription-and-hematopoietic-differentiation-correlate-with-gata2-mutant-disease-phenotypes
#20
C-E Chong, P Venugopal, P H Stokes, Y K Lee, P J Brautigan, D T O Yeung, M Babic, G A Engler, S W Lane, M Klingler-Hoffmann, J M Matthews, R J D'Andrea, A L Brown, C N Hahn, H S Scott
Heterozygous GATA2 mutations underlie an array of complex hematopoietic and lymphatic diseases. Analysis of the literature reporting three recurrent GATA2 germline (g) mutations (gT354M, gR396Q and gR398W) revealed different phenotype tendencies. Although all three mutants differentially predispose to myeloid malignancies, there was no difference in leukemia-free survival for GATA2 patients. Despite intense interest, the molecular pathogenesis of GATA2 mutation is poorly understood. We functionally characterized a GATA2 mutant allelic series representing major disease phenotypes caused by germline and somatic (s) mutations in zinc finger 2 (ZF2)...
June 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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