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https://www.readbyqxmd.com/read/28533818/a-novel-bcr-abl1-fusion-gene-with-genetic-heterogeneity-indicates-a-good-prognosis-in-a-chronic-myeloid-leukemia-case
#1
Fen Zhou, Runming Jin, Yu Hu, Heng Mei
BACKGROUND: Chronic myelogenous leukemia (CML) is a pluripotent hematopoietic stem cell disorder caused by the fusion of the BCR and ABL1 genes. Quantitative RT-PCR (qRT-PCR) is a routinely performed screening technique to identify BCR-ABL1 fusion genes, but a limitation of this method is its inability to recognize novel fusions that have not been previously characterized. Next-generation sequencing (NGS) is an effective and sensitive detection method for the determination of novel BCR-ABL1 fusion genes as well as previously characterized ones...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/28529810/molecular-profiling-a-case-of-zbtb16-rara-acute-promyelocytic-leukemia
#2
Stephen E Langabeer, Lisa Preston, Johanna Kelly, Matt Goodyer, Ezzat Elhassadi, Amjad Hayat
Several variant RARA translocations have been reported in acute promyelocytic leukemia (APL) of which the t(11;17)(q23;q21), which results in a ZBTB16-RARA fusion, is the most widely identified and is largely resistant to therapy with all-trans retinoic acid (ATRA). The clinical course together with the cytogenetic and molecular characterization of a case of ATRA-unresponsive ZBTB16-RARA APL is described. Additional mutations potentially cooperating with the translocation fusion product in leukemogenesis have been hitherto unreported in ZBTB16-RARA APL and were sought by application of a next-generation sequencing approach to detect those recurrently found in myeloid malignancies...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28527383/tributyltin-and-triphenyltin-exposure-promotes-in-vitro-adipogenic-differentiation-but-alters-the-adipocyte-phenotype-in-rainbow-trout
#3
Esmail Lutfi, Natàlia Riera-Heredia, Marlon Córdoba, Cinta Porte, Joaquim Gutiérrez, Encarnación Capilla, Isabel Navarro
Numerous environmental pollutants have been identified as potential obesogenic compounds affecting endocrine signaling and lipid homeostasis. Among them, well-known organotins such as tributyltin (TBT) and triphenyltin (TPT), can be found in significant concentrations in aquatic environments. The aim of the present study was to investigate in vitro the effects of TBT and TPT on the development and lipid metabolism of rainbow trout (Onchorynchus mykiss) primary cultured adipocytes. Results showed that TBT and TPT induced lipid accumulation and slightly enhanced peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT enhancer binding protein alpha (C/EBPα) protein expression when compared to a control, both in the presence or absence of lipid mixture...
May 8, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28504718/a-tumor-suppressor-role-for-c-ebp%C3%AE-in-solid-tumors-more-than-fat-and-blood
#4
REVIEW
A R Lourenço, P J Coffer
The transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) plays a critical role during embryogenesis and is thereafter required for homeostatic glucose metabolism, adipogenesis and myeloid development. Its ability to regulate the expression of lineage-specific genes and induce growth arrest contributes to the terminal differentiation of several cell types, including hepatocytes, adipocytes and granulocytes. CEBPA loss of-function mutations contribute to the development of ~10% of acute myeloid leukemia (AML), stablishing a tumor suppressor role for C/EBPα...
May 15, 2017: Oncogene
https://www.readbyqxmd.com/read/28473620/prognostic-and-biologic-significance-of-long-non-coding-rna-profiling-in-younger-adults-with-cytogenetically-normal-acute-myeloid-leukemia
#5
Dimitrios Papaioannou, Deedra Nicolet, Stefano Volinia, Krzysztof Mrózek, Pearlly Yan, Ralf Bundschuh, Andrew J Carroll, Jessica Kohlschmidt, William Blum, Bayard L Powell, Geoffrey L Uy, Jonathan E Kolitz, Eunice S Wang, Ann-Kathrin Eisfeld, Shelley J Orwick, David M Lucas, Michael A Caligiuri, Richard M Stone, John C Byrd, Ramiro Garzon, Clara D Bloomfield
Long non-coding RNAs are a novel class of RNA molecules, which are increasingly recognized as important molecular players in solid and hematologic malignancies. Herein we investigated whether long non-coding RNA expression is associated with clinical and molecular features, as well as outcome of younger adults (aged <60 years) with de novo cytogenetically normal acute myeloid leukemia. Whole transcriptome profiling (RNA-seq) was performed in a training (n=263) and a validation set (n=114). Using the training set, we identified 24 long non-coding RNAs associated with event-free survival...
May 4, 2017: Haematologica
https://www.readbyqxmd.com/read/28452374/prognostic-significance-of-huntingtin-interacting-protein-1-expression-on-patients-with-acute-myeloid-leukemia
#6
Jinghan Wang, Mengxia Yu, Qi Guo, Qiuling Ma, Chao Hu, Zhixin Ma, Xiufeng Yin, Xia Li, Yungui Wang, Hanzhang Pan, Dongmei Wang, Jiansong Huang, Haitao Meng, Hongyan Tong, Wenbin Qian, Jie Jin
Huntingtin interacting protein 1 (HIP1) is an endocytic protein which is overexpressed in a variety of human cancers and involved in cancer-causing translocation in leukemia. However, the prognostic impact of HIP1 expression on AML remains unclear. In this study, quantification of HIP1 transcript by real-time quantitative PCR in bone marrow blasts was performed in 270 AML patients. As a result, high HIP1 expression was seen more frequently in older patients, M4/M5 morphology and genes of NPM1 and DNMT3A mutations, and underrepresented in favorable karyotype subgroups and CEBPA double allele mutations in our AML patients...
April 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28423525/the-combination-of-circulating-long-noncoding-rnas-ak001058-inhba-as1-mir4435-2hg-and-cebpa-as1-fragments-in-plasma-serve-as-diagnostic-markers-for-gastric-cancer
#7
Dong Ke, Hanwei Li, Yi Zhang, Yinghong An, Hanjiang Fu, Xuedong Fang, Xiaofei Zheng
BACKGROUND: Suitable diagnostic markers for cancers are urgently required in clinical practice. Long non-coding RNAs, which have been reported in many cancer types, are a potential new class of biomarkers for tumor diagnosis. RESULTS: Five lncRNAs, including AK001058, INHBA-AS1, MIR4435-2HG, UCA1 and CEBPA-AS1 were validated to be increased in gastric cancer tissues. Furthermore, we found that plasma level of these five lncRNAs were significantly higher in gastric cancer patients compared with normal controls...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409151/temporal-changes-in-gene-expression-profile-during-mature-adipocyte-dedifferentiation
#8
Julie Anne Côté, Frédéric Guénard, Julie Lessard, Marc Lapointe, Simon Biron, Marie-Claude Vohl, André Tchernof
Objective. To characterize changes in gene expression profile during human mature adipocyte dedifferentiation in ceiling culture. Methods. Subcutaneous (SC) and omental (OM) adipose tissue samples were obtained from 4 participants paired for age and BMI. Isolated adipocytes were dedifferentiated in ceiling culture. Gene expression analysis at days 0, 4, 7, and 12 of the cultures was performed using Affymetrix Human Gene 2.0 STvi arrays. Hierarchical clustering according to similarity of expression changes was used to identify overrepresented functions...
2017: International Journal of Genomics
https://www.readbyqxmd.com/read/28408400/epigenetic-identity-in-aml-depends-on-disruption-of-non-promoter-regulatory-elements-and-is-affected-by-antagonistic-effects-of-mutations-in-epigenetic-modifiers
#9
Jacob Glass, Duane C Hassane, Bas Wouters, Hiroyoshi Kunimoto, Roberto Avellino, Francine E Garrett-Bakelman, Olga A Guryanova, Robert Bowman, Shira Redlich, Andrew Intlekofer, Cem Meydan, Tingting Qin, Mame P Fall, Alicia Alonso, Monica L Guzman, Peter Jm Valk, Craig B Thompson, Ross L Levine, Olivier Elemento, Ruud Delwel, Ari Melnick, Maria E Figueroa
Aberrant DNA methylation of gene promoters is a hallmark of AML. To define more precisely how cytosine methylation is redistributed in AML, we performed base-pair resolution methylome sequencing in 119 patients. We find that leukemic DNA methylation patterning is tightly linked to somatic mutations and primarily driven by regulatory elements outside of promoters and by CpG shores as opposed to CpG islands. Active enhancers displayed much stronger focal differential methylation than promoters and were generally aberrantly hypomethylated except in IDH2 mutant and CEBPA silenced AMLs...
April 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28380436/classification-of-pediatric-acute-myeloid-leukemia-based-on-mirna-expression-profiles
#10
Askar Obulkasim, Jenny E Katsman-Kuipers, Lonneke Verboon, Mathijs Sanders, Ivo Touw, Mojca Jongen-Lavrencic, Rob Pieters, Jan-Henning Klusmann, C Michel Zwaan, Marry M van den Heuvel-Eibrink, Maarten Fornerod
Pediatric acute myeloid leukemia (AML) is a heterogeneous disease with respect to biology as well as outcome. In this study, we investigated whether known biological subgroups of pediatric AML are reflected by a common microRNA (miRNA) expression pattern. We assayed 665 miRNAs on 165 pediatric AML samples. First, unsupervised clustering was performed to identify patient clusters with common miRNA expression profiles. Our analysis unraveled 14 clusters, seven of which had a known (cyto-)genetic denominator. Finally, a robust classifier was constructed to discriminate six molecular aberration groups: 11q23-rearrangements, t(8;21)(q22;q22), inv(16)(p13q22), t(15;17) (q21;q22), NPM1 and CEBPA mutations...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28357685/familial-acute-myeloid-leukemia-and-myelodysplasia-in-hungary
#11
Attila Péter Király, Krisztián Kállay, Ambrus Gángó, Ádám Kellner, Miklós Egyed, Anita Szőke, Richárd Kiss, István Vályi-Nagy, Judit Csomor, András Matolcsy, Csaba Bödör
Although genetic predisposition to haematological malignancies has long been known, genetic testing is not yet the part of the routine diagnostics. In the last ten years, next generation sequencing based studies identified novel germline mutations in the background of familial aggregation of certain haematologic disorders including myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). This is supported by the fact that the myeloid neoplasms with genetic predisposition represent a new category in the revised 2016 World Health Organization classification...
March 29, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28341738/higher-hopx-expression-is-associated-with-distinct-clinical-and-biological-features-and-predicts-poor-prognosis-in-de-novo-acute-myeloid-leukemia
#12
Chien-Chin Lin, Yueh-Chwen Hsu, Yi-Hung Li, Yuan-Yeh Kuo, Hsin-An Hou, Keng-Hsueh Lan, Tsung-Chih Chen, Yi-Shiuan Tzeng, Yi-Yi Kuo, Chein-Jun Kao, Po-Han Chuang, Mei-Hsuan Tseng, Yu-Chiao Chiu, Wen-Chien Chou, Hwei-Fang Tien
Homeodomain-only protein homeobox (HOPX) is the smallest homeodomain protein. It was regarded as a stem cell marker in several non-hematopoietic systems. While the prototypic homeobox genes such as HOX family have been well characterized in acute myeloid leukemia, the clinical and biological implications of HOPX in the disease remain unknown. Thus we analyzed HOPX and global gene expression patterns in 347 newly diagnosed de novo acute myeloid leukemia patients in our institute. We found that higher HOPX expression was closely associated with older age, higher platelet counts, lower white blood cell counts, lower lactate dehydrogenase levels, and mutations in RUNX1, IDH2, ASXL1, and DNMT3A, but negatively associated with acute promyelocytic leukemia, favorable karyotypes, CEBPA double mutations and NPM1 mutation...
March 24, 2017: Haematologica
https://www.readbyqxmd.com/read/28299657/runx1-eto-leukemia
#13
Shan Lin, James C Mulloy, Susumu Goyama
AML1-ETO leukemia is the most common cytogenetic subtype of acute myeloid leukemia, defined by the presence of t(8;21). Remarkable progress has been achieved in understanding the molecular pathogenesis of AML1-ETO leukemia. Proteomic surveies have shown that AML-ETO forms a stable complex with several transcription factors, including E proteins. Genome-wide transcriptome and ChIP-seq analyses have revealed the genes directly regulated by AML1-ETO, such as CEBPA. Several lines of evidence suggest that AML1-ETO suppresses endogenous DNA repair in cells to promote mutagenesis, which facilitates acquisition of cooperating secondary events...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28250006/cebpa-double-mutated-acute-myeloid-leukemia-displays-a-unique-phenotypic-profile-a-reliable-screening-method-and-insight-into-biological-features
#14
Francesco Mannelli, Vanessa Ponziani, Sara Bencini, Maria Ida Bonetti, Matteo Benelli, Ilaria Cutini, Giacomo Gianfaldoni, Barbara Scappini, Fabiana Pancani, Matteo Piccini, Tommaso Rondelli, Roberto Caporale, Anna Maria Grazia Gelli, Benedetta Peruzzi, Marco Chiarini, Erika Borlenghi, Orietta Spinelli, Damiano Giupponi, Pamela Zanghì, Renato Bassan, Alessandro Rambaldi, Giuseppe Rossi, Alberto Bosi
Mutations in CCAAT/enhancer binding protein α (CEBPA) occur in 5-10% of cases of acute myeloid leukemia. CEBPA-double-mutated cases usually bear biallelic N- and C-terminal mutations and are associated with a favorable clinical outcome. Identification of CEBPA mutants is challenging because of the variety of mutations, intrinsic characteristics of the gene and technical issues. Several screening methods (fragment-length analysis, gene expression array) have been proposed especially for large-scale clinical use; although efficient, they are limited by specific concerns...
March 2017: Haematologica
https://www.readbyqxmd.com/read/28249600/identification-of-somatic-mutations-using-whole-exome-sequencing-in-korean-patients-with-acute-myeloid-leukemia
#15
Seong Gu Heo, Youngil Koh, Jong Kwang Kim, Jongsun Jung, Hyung-Lae Kim, Sung-Soo Yoon, Ji Wan Park
BACKGROUND: Acute myeloid leukemia (AML) is a biologically and clinically heterogeneous cancer of the bone marrow that is characterized by the rapid growth of abnormal myeloid cells. METHODS: We performed a mutational analysis to identify AML somatic mutations using the whole-exome sequencing data of 36 tumor-normal sample pairs from Korean patients with de novo AML. We explored the functional impact of the genes identified in the mutational analyses through an integrated Gene Ontology (GO) and pathway analysis...
March 1, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28210006/a-novel-lsd1-inhibitor-ncd38-ameliorates-mds-related-leukemia-with-complex-karyotype-by-attenuating-leukemia-programs-via-activating-super-enhancers
#16
N Sugino, M Kawahara, G Tatsumi, A Kanai, H Matsui, R Yamamoto, Y Nagai, S Fujii, Y Shimazu, M Hishizawa, T Inaba, A Andoh, T Suzuki, A Takaori-Kondo
Lysine-specific demethylase 1 (LSD1) regulates gene expression by affecting histone modifications and is a promising target for acute myeloid leukemia (AML) with specific genetic abnormalities. Novel LSD1 inhibitors, NCD25 and NCD38, inhibited growth of MLL-AF9 leukemia as well as erythroleukemia, megakaryoblastic leukemia and myelodysplastic syndromes (MDS) overt leukemia cells in the concentration range that normal hematopoiesis was spared. NCD25 and NCD38 invoked the myeloid development programs, hindered the MDS and AML oncogenic programs, and commonly upregulated 62 genes in several leukemia cells...
February 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28203345/sweet-s-syndrome-associated-with-clonal-hematopoiesis-of-indeterminate-potential-responsive-to-5-azacitidine
#17
REVIEW
George Yaghmour, Eric Wiedower, Bassam Yaghmour, Sara Nunnery, Eric Duncavage, Mike G Martin
Sweet's syndrome (SS) is a rare condition characterized by the abrupt appearance of painful skin lesions due to neutrophilic dermal infiltration. Hematologic neoplasms, particularly acute myeloid leukemia (AML) and myelodysplastic syndromes (MDSs), have been commonly reported in association with SS. Clonal hematopoiesis of indeterminate potential (CHIP) is an emerging entity that is a precursor state to myeloid neoplasms. CHIP has not been previously associated with SS. We report the case of a 71-year-old man who presented with recurrent, painful edematous and erythematous papules and nodules for 18 months despite treatment with corticosteroids...
February 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28197208/molecular-mutations-and-their-cooccurrences-in-cytogenetically-normal-acute-myeloid-leukemia
#18
REVIEW
Mengning Wang, Chuanwei Yang, Le Zhang, Dale G Schaar
Adult acute myeloid leukemia (AML) clinically is a disparate disease that requires intensive treatments ranging from chemotherapy alone to allogeneic hematopoietic cell transplantation (allo-HCT). Historically, cytogenetic analysis has been a useful prognostic tool to classify patients into favorable, intermediate, and unfavorable prognostic risk groups. However, the intermediate-risk group, consisting predominantly of cytogenetically normal AML (CN-AML), itself exhibits diverse clinical outcomes and requires further characterization to allow for more optimal treatment decision-making...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28194057/clinical-characteristics-and-prognosis-of-167-cases-of-acute-erythroleukemia
#19
Zhi-Qiang Ma, Ji-Hong Pan, Da-Xin Jing, Chong-Yan Xu
To observe the biological characteristic and the prognoses in patients with acute erythroleukemia (AEL). The results of 167 patients with newly diagnosed AEL, from January 2004 and June 2014 in the department of Hematology, Shandong Province Chinese Medicine Hospital, were reviewed by morphology, immunology, cytogenetics, molecular biology. Flow cytometry analysis indicated that CD13 (96.1 %), CD33 (95.1 %), CD117 (87.4 %) and CD34 (79.4 %) were highly expressed in AEL. 56 of 148 (37.8 %) AEL patients had a variety of cytogenetic abnormalities, 27 of 148 (18...
March 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28186500/evi2b-is-a-c-ebp%C3%AE-target-gene-required-for-granulocytic-differentiation-and-functionality-of-hematopoietic-progenitors
#20
Polina Zjablovskaja, Miroslava Kardosova, Petr Danek, Pavla Angelisova, Touati Benoukraf, Alexander A Wurm, Tomas Kalina, Stephanie Sian, Martin Balastik, Ruud Delwel, Tomas Brdicka, Daniel G Tenen, Gerhard Behre, Fréderic Fiore, Bernard Malissen, Vaclav Horejsi, Meritxell Alberich-Jorda
Development of hematopoietic populations through the process of differentiation is critical for proper hematopoiesis. The transcription factor CCAAT/enhancer binding protein alpha (C/EBPα) is a master regulator of myeloid differentiation, and the identification of C/EBPα target genes is key to understand this process. Here we identified the Ecotropic Viral Integration Site 2B (EVI2B) gene as a direct target of C/EBPα. We showed that the product of the gene, the transmembrane glycoprotein EVI2B (CD361), is abundantly expressed on the surface of primary hematopoietic cells, the highest levels of expression being reached in mature granulocytes...
April 2017: Cell Death and Differentiation
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