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https://www.readbyqxmd.com/read/29773598/concomitant-wt1-mutations-predict-poor-prognosis-in-acute-myeloid-leukemia-patients-with-double-mutant-cebpa
#1
Feng-Ming Tien, Hsin-An Hou, Jih-Luh Tang, Yuan-Yeh Kuo, Chien-Yuan Chen, Cheng-Hong Tsai, Ming Yao, Chien-Ting Lin, Chi-Cheng Li, Shang-Yi Huang, Bor-Sheng Ko, Szu-Chun Hsu, Shang-Ju Wu, Jia-Hau Liu, Sheng-Chieh Chou, Woei Tsay, Mei-Hsuan Tseng, Ming-Chih Liu, Chia-Wen Liu, Liang-In Lin, Wen-Chien Chou, Hwei-Fang Tien
No abstract text is available yet for this article.
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29766829/acute-myeloid-leukemia-diagnosis-and-management-based-on-current-molecular-genetics-approach
#2
E Suguna, R Farhana, E Kanimozhi, P SaiKumar, G Kumaramanickavel, Chitralekha Sai Kumar
Background &Objective: Acute myeloid leukemia (AML) is characterized by accumulation of ?20% myeloid premature blast cells in the bone marrow and most often found in the peripheral blood. AML is generally classified based on two groups, namely, French-American-British (FAB) and World Health Organization (WHO) systems. For better clinical management, cytogenetic findings in AML are necessary and in patients with normal karyotypes, molecular analysis becomes critical. Mutations of certain genes like Nucleophosmin 1gene (NPM1), Fms-related Tyrosine Kinase 3 (FLT3), CCAAT/Enhancer Binding Protein Alpha (CEBPA), Runt-related transcription factor 1(RUNX1), and Mixed Lineage Leukemia (MLL) play a crucial role in the risk management and clinical stratification of AML patients...
May 15, 2018: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/29748795/role-of-lncrnas-as-prognostic-markers-of-hepatic-cancer-and-potential-therapeutic-targeting-by-s-adenosylmethionine-via-inhibiting-pi3k-akt-signaling-pathways
#3
Kadry M Sadek, Mohamed A Lebda, Nasr E Nasr, Sherif M Nasr, Yasser El-Sayed
Hepatic cancer (HCC) is a well-identified dilemma throughout the world, and hence, the molecular mechanisms and strategy for preventive protection against this malignancy are critical. S-adenosylmethionine (SAM) is a unique methyl granter in vast reactions, including DNA methylation, and secures the genome against hypomethylation, which is a hallmark of tumors. Consequently, SAM may control the rate of gene expression. The objective of this investigation was to evaluate the expression of long noncoding RNAs (lncRNAs) transcript involved in hepatic tumorigenesis, including additional coding CEBPA (ecCEBPA) and urothelial carcinoma related 1 (UCA1), antioxidant enzymes transcripts, and relevant signaling pathway in diethylnitrosamine (DEN)-prompted HCC along with their conceivable targeting by SAM at different stages of HCC in rats...
May 10, 2018: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29727824/chinese-and-europeans-with-acute-myeloid-leukemia-have-discordant-mutation-topographies
#4
Min Zhang, Jiawei Yin, Qinghua He, Fan Zhang, Hongyu Huang, Biao Wu, Xuedong Wang, Hong Liu, Hongchao Yin, Yan Zeng, Robert Peter Gale, Depei Wu, Bin Yin
Although the topography of mutations in persons of predominately European-descent with acute myeloid leukemia (AML) is well-described this is less so in Asians. We studied AML-related mutations in 289 consecutive Chinese (mostly Han) with newly-diagnosed de novo AML. Full-length coding sequence of NPM1 and CEBPA, IDH1 and IDH2 hotspot mutations and WT1 mutations in exons 7 and 9 were analyzed by PCR as were correlations with clinical and laboratory variables. CEBPA mutations were detected in 20% of subjects (95% confidence interval [CI] 15, 25%), NPM1 mutations in 20% (15, 25%), IDH1 mutations in 4% (1, 6%), IDH2 mutations in 11% (7, 15%) and WT1 mutations in 6% (3, 9%)...
April 22, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29624746/hyperleukocytosis-is-associated-with-distinct-genetic-alterations-and-is-an-independent-poor-risk-factor-in-de-novo-acute-myeloid-leukemia-patients
#5
Feng-Ming Tien, Hsin-An Hou, Cheng-Hong Tsai, Jih-Luh Tang, Chien-Yuan Chen, Yuan-Yeh Kuo, Chi-Cheng Li, Chien-Ting Lin, Ming Yao, Shang-Yi Huang, Bor-Sheng Ko, Szu-Chun Hsu, Shang-Ju Wu, Woei Tsay, Mei-Hsuan Tseng, Ming-Chih Liu, Chia-Wen Liu, Liang-In Lin, Wen-Chien Chou, Hwei-Fang Tien
OBJECTIVES: Acute myeloid leukemia (AML) with hyperleukocytosis (HL) is intuitively thought as a unique group with dismal prognosis. However, comprehensive studies regarding the genetic landscape and clinical outcome in this group of patients are limited. METHODS: 693 newly diagnosed de novo non-M3 AML patients were consecutively enrolled. We compared relevant mutations in 20 genes between AML patients with or without HL and exposed their prognostic implications...
April 6, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29622865/the-synonymous-isocitrate-dehydrogenase-1-315c-t-snp-confers-an-adverse-prognosis-in-egyptian-adult-patients-with-npm1-cebpa-negative-acute-myeloid-leukemia
#6
Mohamed A M Ali, Emad K Ahmed, Magda M A Assem, Reham Helwa
Although the clinical features of isocitrate dehydrogenase ( IDH ) genetic aberrations have been well-characterized in acute myeloid leukemia (AML), definitive information on their prognostic significance is lacking. We aimed to explore the prognostic significance of IDH gene alterations in an Egyptian cohort of adult patients with de novo AML. Diagnostic peripheral blood samples from 51 AML patients were analyzed for the presence of mutations/SNPs in exon 4 of IDH1 and IDH2 genes using polymerase chain reaction amplification followed by direct sequencing...
April 2018: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/29593668/simulation-study-of-cdna-dataset-to-investigate-possible-association-of-differentially-expressed-genes-of-human-thp1-monocytic-cells-in-cancer-progression-affected-by-bacterial-shiga-toxins
#7
Syed A Muhammad, Jinlei Guo, Thanh M Nguyen, Xiaogang Wu, Baogang Bai, X Frank Yang, Jake Y Chen
Shiga toxin (Stxs) is a family of structurally and functionally related bacterial cytotoxins produced by Shigella dysenteriae serotype 1 and shigatoxigenic group of Escherichia coli that cause shigellosis and hemorrhagic colitis, respectively. Until recently, it has been thought that Stxs only inhibits the protein synthesis and induces expression to a limited number of genes in host cells, but recent data showed that Stxs can trigger several signaling pathways in mammalian cells and activate cell cycle and apoptosis...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29573577/mutation-profile-and-associated-clinical-features-in-chinese-patients-with-cytogenetically-normal-acute-myeloid-leukemia
#8
S Wang, Y-X Zhang, T Huang, J-N Sui, J Lu, X-J Chen, K-K Wang, X-D Xi, J-M Li, J-Y Huang, B Chen
INTRODUCTION: Cytogenetically normal acute myeloid leukemia (CN-AML), which accounted for nearly half of total AML patients, is a highly heterogeneous subset of AML. The specific genetic profile and the ethnic features of CN-AML are worth to be studied. METHODS: Using deep sequencing technology, we detected the mutation pattern of 39 genes in 152 Chinese CN-AML patients and analyzed their clinical features. RESULTS: A total of 503 mutations of 39 genes were identified in 145 (95...
March 24, 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29541391/acute-myeloid-leukemia-with-t-4-12-q12-p13-an-aggressive-disease-with-frequent-involvement-of-pdgfra-and-etv6
#9
Jingyi Li, Jie Xu, Lynne V Abruzzo, Guilin Tang, Shaoying Li, M James You, Gary Lu, Elias J Jabbour, Qi Deng, Carlos E Bueso-Ramos, L Jeffrey Medeiros, C Cameron Yin
We describe the clinical, morphologic, immunophenotypic and molecular genetic features of 15 cases of acute myeloid leukemia (AML) with t(4;12)(q12;p13). There were 9 men and 6 women, with a median age of 50 years (range, 17-76). Most patients had hypercellular bone marrow with a median blast count of 58% and multilineage dysplasia. Flow cytometry analysis showed myeloid lineage with blasts positive for CD13, CD33, CD34, CD38, CD117 and HLA-DR. Interestingly, aberrant CD7 expression was detected in 12/14 cases, and myeloperoxidase was either negative (3/15) or positive in only a small subset of the blasts (12/15)...
February 16, 2018: Oncotarget
https://www.readbyqxmd.com/read/29534404/-study-on-relationship-between-set-gene-expression-and-clinical-manifestations-in-bone-marrow-of-patients-with-acute-myelogenous-leukemia
#10
Y Liu, T Lei, Y Shi, X Y Wang, M L Sun, W X Fan, Z N Zhang, M Jiang
Objective: To explore the expression and significance of Set gene in Acute myeloid leukemia (AML) patients , and to analyze its effect for the prognosis of AML. Methods: The level of Set gene expression was detected by real-time PCR in 59 AML patients and 20 heathy people. The mutations in C-kit 8/17 gene, NPM1 gene and FLT3-TKD/ITD gene in 59 AML patients were detected by direct sequencing. Results: The level of Set gene expression[1.41(0.41-3.31)]was significantly higher in 59 AML patients.The expression of Set gene was correlated with the percentage of marrow blasts and CR in AML patients ( P =0...
March 6, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29515250/prognostic-significance-of-microrna-99a-in-acute-myeloid-leukemia-patients-undergoing-allogeneic-hematopoietic-stem-cell-transplantation
#11
Zhiheng Cheng, Lei Zhou, Kai Hu, Yifeng Dai, Yifan Pang, Hongmian Zhao, Sun Wu, Tong Qin, Yu Han, Ning Hu, Li Chen, Chao Wang, Yijie Zhang, Depei Wu, Xiaoyan Ke, Jinlong Shi, Lin Fu
Overexpression of microRNA-99a (miR-99a) have been associated with adverse prognosis in acute myeloid leukemia (AML). Nevertheless, whether it also predicts poor outcome in post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) AML patients remains unclear. To further elucidate the prognostic value of miR-99a, 74 AML patients with miR-99a expression report who underwent allo-HSCT from The Cancer Genome Atlas database were identified and grouped into either miR-99ahigh or miR-99alow based on their miR-99a expression levels relative to the median...
March 7, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29511346/gene-activation-of-cebpa-using-sarna-preclinical-studies-of-the-first-in-human-sarna-drug-candidate-for-liver-cancer
#12
Vikash Reebye, Kai-Wen Huang, Vivian Lin, Sheba Jarvis, Pedro Cutilas, Stephanie Dorman, Simona Ciriello, Pinelopi Andrikakou, Jon Voutila, Pal Saetrom, Paul J Mintz, Isabella Reccia, John J Rossi, Hans Huber, Robert Habib, Nikos Kostomitsopoulos, David C Blakey, Nagy A Habib
Liver diseases are a growing epidemic worldwide. If unresolved, liver fibrosis develops and can lead to cirrhosis and clinical decompensation. Around 5% of cirrhotic liver diseased patients develop hepatocellular carcinoma (HCC), which in its advanced stages has limited therapeutic options and negative survival outcomes. CEPBA is a master regulator of hepatic function where its expression is known to be suppressed in many forms of liver disease including HCC. Injection of MTL-CEBPA, a small activating RNA oligonucleotide therapy (CEBPA-51) formulated in liposomal nanoparticles (NOV340- SMARTICLES) upregulates hepatic CEBPA expression...
March 7, 2018: Oncogene
https://www.readbyqxmd.com/read/29484393/spontaneous-adipogenic-differentiation-potential-of-adipose%C3%A2-derived-stem-cells-decreased-with-increasing-cell-passages
#13
Duo Yang, Na Li, Guoying Zhang
Primary adipose-derived stem cells (ADSCs) are a mixture of cell types including preadipocytes having the ability to spontaneously differentiate into adipocytes. The aim of the present study was to compare the spontaneous adipogenic differentiation potential of ADSCs at different passages to determine whether it decreased with continuous cell passages. Mouse ADSCs (mADSCs) were harvested and cells from passages 1 to 5 were used for experiments. The proliferation of mADSCs at different passages was tested using the cell counting kit‑8 assay...
April 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29483711/universal-genetic-testing-for-inherited-susceptibility-in-children-and-adults-with-myelodysplastic-syndrome-and-acute-myeloid-leukemia-are-we-there-yet
#14
REVIEW
Kiran Tawana, Michael W Drazer, Jane E Churpek
Comprehensive genomic profiling of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) cases have enabled the detection and differentiation of driver and subclonal mutations, informed risk prognostication, and defined targeted therapies. These insights into disease biology, and management have made multigene-acquired mutation testing a critical part of the diagnostic assessment of patients with sporadic MDS and AML. More recently, our understanding of the role of an increasing number of inherited genetic factors on MDS/AML risk and management has rapidly progressed...
February 27, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29467326/loss-of-epigenetic-regulator-tet2-and-oncogenic-kit-regulate-myeloid-cell-transformation-via-pi3k-pathway
#15
Lakshmi Reddy Palam, Raghuveer Singh Mali, Baskar Ramdas, Sridhar Nonavinkere Srivatsan, Valeria Visconte, Ramon V Tiu, Bart Vanhaesebroeck, Axel Roers, Alexander Gerbaulet, Mingjiang Xu, Sarath Chandra Janga, Clifford M Takemoto, Sophie Paczesny, Reuben Kapur
Mutations in KIT and TET2 are associated with myeloid malignancies. We show that loss of TET2-induced PI3K activation and -increased proliferation is rescued by targeting the p110α/δ subunits of PI3K. RNA-Seq revealed a hyperactive c-Myc signature in Tet2-/- cells, which is normalized by inhibiting PI3K signaling. Loss of TET2 impairs the maturation of myeloid lineage-derived mast cells by dysregulating the expression of Mitf and Cebpa, which is restored by low-dose ascorbic acid and 5-azacytidine. Utilizing a mouse model in which the loss of TET2 precedes the expression of oncogenic Kit, similar to the human disease, results in the development of a non-mast cell lineage neoplasm (AHNMD), which is responsive to PI3K inhibition...
February 22, 2018: JCI Insight
https://www.readbyqxmd.com/read/29464001/piwil3-oip5-as1-mir-367-3p-cebpa-feedback-loop-regulates-the-biological-behavior-of-glioma-cells
#16
Xiaobai Liu, Jian Zheng, Yixue Xue, Hai Yu, Wei Gong, Ping Wang, Zhen Li, Yunhui Liu
Rationale: PIWI-interacting RNAs (piRNAs), a class of newly discovered small RNA molecules that function by binding to the Argonaute protein family (i.e., the PIWIL protein subfamily), and long noncoding RNAs (lncRNA) are implicated in several cancers. However, the detailed roles of ncRNAs in glioma remain unclear. Methods: The expression of PIWIL3, piR-30188, OIP5-AS1, miR-367, CEBPA and TRAF4 were measured in glioma tissues and cells. The role of PIWIL3/OIP5-AS1/miR-367-3p/CEBPA feedback loop was evaluated in cell and animal models...
2018: Theranostics
https://www.readbyqxmd.com/read/29444854/bet-bromodomain-proteins-regulate-enhancer-function-during-adipogenesis
#17
Jonathan D Brown, Zachary B Feldman, Sean P Doherty, Jaime M Reyes, Peter B Rahl, Charles Y Lin, Quanhu Sheng, Qiong Duan, Alexander J Federation, Andrew L Kung, Saptarsi M Haldar, Richard A Young, Jorge Plutzky, James E Bradner
Developmental transitions are guided by master regulatory transcription factors. During adipogenesis, a transcriptional cascade culminates in the expression of PPARγ and C/EBPα, which orchestrate activation of the adipocyte gene expression program. However, the coactivators controlling PPARγ and C/EBPα expression are less well characterized. Here, we show the bromodomain-containing protein, BRD4, regulates transcription of PPARγ and C/EBPα. Analysis of BRD4 chromatin occupancy reveals that induction of adipogenesis in 3T3L1 fibroblasts provokes dynamic redistribution of BRD4 to de novo super-enhancers proximal to genes controlling adipocyte differentiation...
February 27, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29435155/assessment-of-a-new-genomic-classification-system-in-acute-myeloid-leukemia-with-a-normal-karyotype
#18
Jae-Sook Ahn, Hyeoung-Joon Kim, Yeo-Kyeoung Kim, Seung-Shin Lee, Seo-Yeon Ahn, Sung-Hoon Jung, Deok-Hwan Yang, Je-Jung Lee, Hee Jeong Park, Ja-Yeon Lee, Seung Hyun Choi, Chul Won Jung, Jun-Ho Jang, Hee Je Kim, Joon Ho Moon, Sang Kyun Sohn, Yoo Jin Lee, Jong-Ho Won, Sung-Hyun Kim, Zhaolei Zhang, TaeHyung Kim, Dennis Dong Hwan Kim
This study was performed to assess if a recently recommended genomic classification is predictive in patients with normal-karyotype (NK) acute myeloid leukemia (AML). A total of 393 patients were included. Analysis of genetic mutations was performed using targeted resequencing with an Illumina Hiseq 2000. We identified driver mutations across 40 genes, with one or more driver mutations identified in 95.7% of patients. The molecular subclassification was as follows: 34.6% patients (n = 136) with AML with the NPM1 mutation, 10...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29431622/c-ebp%C3%AE-overrides-epigenetic-reprogramming-by-oncogenic-transcription-factors-in-acute-myeloid-leukemia
#19
Justin Loke, Paulynn Suyin Chin, Peter Keane, Anna Pickin, Salam A Assi, Anetta Ptasinska, Maria Rosaria Imperato, Peter N Cockerill, Constanze Bonifer
Acute myeloid leukemia (AML) is a heterogeneous disease caused by recurrent mutations in the transcription regulatory machinery, resulting in abnormal growth and a block in differentiation. One type of recurrent mutations affects RUNX1 , which is subject to mutations and translocations, the latter giving rise to fusion proteins with aberrant transcriptional activities. We recently compared the mechanism by which the products of the t(8;21) and the t(3;21) translocation RUNX1-ETO and RUNX1-EVI1 reprogram the epigenome...
February 13, 2018: Blood Advances
https://www.readbyqxmd.com/read/29402726/high-expression-of-tet1-predicts-poor-survival-in-cytogenetically-normal-acute-myeloid-leukemia-from-two-cohorts
#20
Jinghan Wang, Fenglin Li, Zhixin Ma, Mengxia Yu, Qi Guo, Jiansong Huang, Wenjuan Yu, Yungui Wang, Jie Jin
Ten-Eleven-Translocation 1 (TET1) plays a role in the DNA methylation process and gene activation. Recent reports suggest TET1 acts as an oncogene in leukemia development. However, the clinical relevance and biological insight of TET1 expression in cytogenetically normal acute myeloid leukemia (CN-AML) is unknown. In this study, quantification of TET1 transcript by real-time quantitative PCR in bone marrow blasts was performed in 360 CN-AML patients. As a result, high TET1 expression was more common in M0/M1 morphology and genes of NPM1 mutations, and underrepresented in CEBPA double allele mutations in our AML patients...
February 2018: EBioMedicine
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