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https://www.readbyqxmd.com/read/28736168/light-dependent-degradation-of-pif3-by-scf-ebf1-2-promotes-a-photomorphogenic-response-in-arabidopsis
#1
Jie Dong, Weimin Ni, Renbo Yu, Xing Wang Deng, Haodong Chen, Ning Wei
Plant seedlings emerging from darkness into the light environment undergo photomorphogenesis, which enables autotrophic growth with optimized morphology and physiology. During this transition, plants must rapidly remove photomorphogenic repressors accumulated in the dark. Among them is PHYTOCHROME-INTERACTING FACTOR 3 (PIF3), a key transcription factor promoting hypocotyl growth. Here we report that, in response to light activation of phytochrome photoreceptors, EIN3-BINDING F BOX PROTEINs (EBFs) 1 and 2 mediate PIF3 protein degradation in a manner dependent on light-induced phosphorylation of PIF3...
July 18, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28704388/the-mir-23a-27a-24-2-microrna-cluster-buffers-transcription-and-signaling-pathways-during-hematopoiesis
#2
Jeffrey L Kurkewich, Justin Hansen, Nathan Klopfenstein, Helen Zhang, Christian Wood, Austin Boucher, Joseph Hickman, David E Muench, H Leighton Grimes, Richard Dahl
MicroRNA cluster mirn23a has previously been shown to promote myeloid development at the expense of lymphoid development in overexpression and knockout mouse models. This polarization is observed early in hematopoietic development, with an increase in common lymphoid progenitors (CLPs) and a decrease in all myeloid progenitor subsets in adult bone marrow. The pool size of multipotential progenitors (MPPs) is unchanged; however, in this report we observe by flow cytometry that polarized subsets of MPPs are changed in the absence of mirn23a...
July 13, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28692033/spontaneous-loss-of-b-lineage-transcription-factors-leads-to-pre-b-leukemia-in-ebf1-bcl-xl-tg-mice
#3
J A Ramírez-Komo, M A Delaney, D Straign, K Lukin, M Tsang, B M Iritani, J Hagman
Early B-cell factor 1 (EBF1) plays a central role in B-cell lineage specification and commitment. Loss of this critical transcription factor is strongly associated with high-risk, relapsed and therapy-resistant B-cell-acute lymphoblastic leukemia, especially in children. However, Ebf1 haploinsufficient mice exhibit a normal lifespan. To determine whether prolonged survival of B cells would enable tumorigenesis in Ebf1 haploinsufficient animals, we generated Ebf1(+/-)Bcl-xL(Tg) mice, which express the anti-apoptotic factor Bcl-xL in B cells...
July 10, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28655536/b-cell-identity-as-a-metabolic-barrier-against-malignant-transformation
#4
REVIEW
Lai N Chan, Markus Müschen
B-lineage and myeloid leukemia cells are often transformed by the same oncogenes, but have different biological and clinical characteristics. Although B-lineage acute lymphoblastic leukemia (B-ALL) cells are characterized by a state of chronic energy deficit, myeloid leukemia cells show abundant energy reserve. Interestingly, fasting has been demonstrated to inhibit selectively the development of B-ALL but not myeloid leukemia, further suggesting that lineage identity may be linked to divergent metabolic states in hematopoietic malignancies...
June 24, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28631637/an-integrated-genomic-profile-that-includes-copy-number-alterations-is-highly-predictive-of-minimal-residual-disease-status-in-childhood-precursor-b-lineage-acute-lymphoblastic-leukemia
#5
Nikhil Patkar, P G Subramanian, Prashant Tembhare, Sneha Mandalia, Gaurav Chaterjee, Nikhil Rabade, Rohan Kodgule, Karishma Chopra, Asma Bibi, Swapnali Joshi, Shruti Chaudhary, Russel Mascerhenas, Pratibha Kadam-Amare, Gaurav Narula, Brijesh Arora, Shripad Banavali, Sumeet Gujral
INTRODUCTION: Copy number alterations (CNA) have been described in childhood precursor B-lineage acute lymphoblastic leukemia (B-ALL) which in conjunction with chromosomal abnormalities drive leukemogenesis. There is no consensus on the clinical incorporation of CNA in B-ALL. An integrated genomic classification (IGC) has been proposed which includes CNA and cytogenetics. METHODS: We correlated this IGC with immunophenotypic minimal residual disease (MRD) as well as other standard criteria for 245 patients of B-ALL such as National Cancer Institute (NCI) risk, D+8 prednisolone response, cytogenetics, and ploidy status...
April 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/28630421/a-genome-wide-association-study-of-anorexia-nervosa-suggests-a-risk-locus-implicated-in-dysregulated-leptin-signaling
#6
Dong Li, Xiao Chang, John J Connolly, Lifeng Tian, Yichuan Liu, Elizabeth J Bhoj, Nora Robinson, Debra Abrams, Yun R Li, Jonathan P Bradfield, Cecilia E Kim, Jin Li, Fengxiang Wang, James Snyder, Maria Lemma, Cuiping Hou, Zhi Wei, Yiran Guo, Haijun Qiu, Frank D Mentch, Kelly A Thomas, Rosetta M Chiavacci, Roger Cone, Bingshan Li, Patrick A Sleiman, Hakon Hakonarson
We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 × 10(-7); OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28597942/copy-number-alterations-determined-by-single-nucleotide-polymorphism-array-testing-in-the-clinical-laboratory-are-indicative-of-gene-fusions-in-pediatric-cancer-patients
#7
Tracy M Busse, Jacquelyn J Roth, Donna Wilmoth, Luanne Wainwright, Laura Tooke, Jaclyn A Biegel
Gene fusions resulting from structural rearrangements are an established mechanism of tumorigenesis in pediatric cancer. In this clinical cohort, 1,350 single nucleotide polymorphism (SNP)-based chromosomal microarrays from 1,211 pediatric cancer patients were evaluated for copy number alterations (CNAs) associated with gene fusions. Karyotype or fluorescence in situ hybridization studies were performed in 42% of the patients. Ten percent of the bone marrow or solid tumor specimens had SNP array-associated CNAs suggestive of a gene fusion...
June 9, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28579594/exploration-of-underlying-mechanism-of-anti-adipogenic-activity-of-sulfuretin
#8
Ramakanta Lamichhane, Se-Gun Kim, Sona Kang, Kyung-Hee Lee, Prakash Raj Pandeya, Hyun-Ju Jung
Sulfuretin is a natural flavonoid found in the plant Rhus verniciflua Stokes. The plant has been traditionally used as medicinal agent for antiviral, cathartic, diaphoretic, anti-rheumatic and sedative activities in East Asia. In this study we isolated and identified sulfuretin from R. verniciflua and investigated its anti-adipogenic activity against 3T3-L1 preadipocytes cells. We evaluated the effects of sulfuretin on the adipogenic transcription factors like PPARγ, C/EBPα, FAS, Fabp4, adiponectin and Zfp521 by gene expression (real-time QPCR) and Western blot analysis...
June 3, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28555080/deregulation-of-kinase-signaling-and-lymphoid-development-in-ebf1-pdgfrb-all-leukemogenesis
#9
S J Welsh, M L Churchman, M Togni, C G Mullighan, J Hagman
The chimeric fusion oncogene early B-cell factor 1-platelet-derived growth factor receptor-β (EBF1-PDGFRB) is a recurrent lesion observed in Philadelphia-like B-acute lymphoblastic leukemia (B-ALL) and is associated with particularly poor prognosis. While it is understood that this fusion activates tyrosine kinase signaling, the mechanisms of transformation and importance of perturbation of EBF1 activity remain unknown. EBF1 is a nuclear transcription factor required for normal B-lineage specification, commitment and development...
May 30, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28542178/uncovering-direct-and-indirect-molecular-determinants-of-chromatin-loops-using-a-computational-integrative-approach
#10
Raphaël Mourad, Lang Li, Olivier Cuvier
Chromosomal organization in 3D plays a central role in regulating cell-type specific transcriptional and DNA replication timing programs. Yet it remains unclear to what extent the resulting long-range contacts depend on specific molecular drivers. Here we propose a model that comprehensively assesses the influence on contacts of DNA-binding proteins, cis-regulatory elements and DNA consensus motifs. Using real data, we validate a large number of predictions for long-range contacts involving known architectural proteins and DNA motifs...
May 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28533268/the-transcription-factor-gli3-promotes-b-cell-development-in-fetal-liver-through-repression-of-shh
#11
Anisha Solanki, Ching-In Lau, José Ignacio Saldaña, Susan Ross, Tessa Crompton
Before birth, B cells develop in the fetal liver (FL). In this study, we show that Gli3 activity in the FL stroma is required for B cell development. In the Gli3-deficient FL, B cell development was reduced at multiple stages, whereas the Sonic hedgehog (Hh [Shh])-deficient FL showed increased B cell development, and Gli3 functioned to repress Shh transcription. Use of a transgenic Hh-reporter mouse showed that Shh signals directly to developing B cells and that Hh pathway activation was increased in developing B cells from Gli3-deficient FLs...
July 3, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28487885/novel-de-novo-variant-in-ebf3-is-likely-to-impact-dna-binding-in-a-patient-with-a-neurodevelopmental-disorder-and-expanded-phenotypes-patient-report-in-silico-functional-assessment-and-review-of-published-cases
#12
Patrick R Blackburn, Sarah S Barnett, Michael T Zimmermann, Margot A Cousin, Charu Kaiwar, Filippo Pinto E Vairo, Zhiyv Niu, Matthew J Ferber, Raul A Urrutia, Duygu Selcen, Eric W Klee, Pavel N Pichurin
Pathogenic variants in EBF3 were recently described in three back-to-back publications in association with a novel neurodevelopmental disorder characterized by intellectual disability, speech delay, ataxia, and facial dysmorphisms. In this report, we describe an additional patient carrying a de novo missense variant in EBF3 (c.487C>T, p.(Arg163Trp)) that falls within a conserved residue in the zinc knuckle motif of the DNA binding domain. Without a solved structure of the DNA binding domain, we generated a homology-based atomic model and performed molecular dynamics simulations for EBF3, which predicted decreased DNA affinity for p...
May 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28476192/gene-expression-profiling-of-acute-lymphoblastic-leukemia-in-children-with%C3%A2-very-early-relapse
#13
MULTICENTER STUDY
Juan Carlos Núñez-Enríquez, Diego Alberto Bárcenas-López, Alfredo Hidalgo-Miranda, Elva Jiménez-Hernández, Vilma Carolina Bekker-Méndez, Janet Flores-Lujano, Karina Anastacia Solis-Labastida, Gabriela Bibiana Martínez-Morales, Fausto Sánchez-Muñoz, Laura Eugenia Espinoza-Hernández, Martha Margarita Velázquez-Aviña, Laura Elizabeth Merino-Pasaye, Alejandra Jimena García Velázquez, María Luisa Pérez-Saldívar, Raúl Mojica-Espinoza, Julián Ramírez-Bello, Silvia Jiménez-Morales, Juan Manuel Mejía-Aranguré
BACKGROUND AND AIMS: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer worldwide. Mexican patients have high mortality rates, low frequency of good prognosis biomarkers (i.e., ETV6-RUNX1) and a high proportion is classified at the time of diagnosis with a high risk to relapse according to clinical features. In addition, very early relapses are more frequently observed than in other populations. The aim of the study was to identify new potential biomarkers associated with very early relapse in Mexican ALL children through transcriptome analysis...
November 2016: Archives of Medical Research
https://www.readbyqxmd.com/read/28463873/transcriptional-circuits-in-b-cell-transformation
#14
Yeguang Hu, Toshimi Yoshida, Katia Georgopoulos
PURPOSE OF REVIEW: Loss of IKAROS in committed B cell precursors causes a block in differentiation while at the same time augments aberrant cellular properties, such as bone marrow stromal adhesion, self-renewal and resistance to glucocorticoid-mediated cell death. B cell acute lymphoblastic leukaemias originating from these early stages of B cell differentiation and associated with IKAROS mutations share a high-risk cellular phenotype suggesting that deregulation of IKAROS-based mechanisms cause a highly malignant disease process...
July 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28439887/clinical-significance-of-recurrent-copy-number-aberrations-in-b-lineage-acute-lymphoblastic-leukaemia-without-recurrent-fusion-genes-across-age-cohorts
#15
Monica Messina, Sabina Chiaretti, Anna Lucia Fedullo, Alfonso Piciocchi, Maria Cristina Puzzolo, Alessia Lauretti, Valentina Gianfelici, Valerio Apicella, Paola Fazi, Geertruy Te Kronnie, Anna Maria Testi, Antonella Vitale, Anna Guarini, Robin Foà
Copy number aberrations (CNAs) represent cooperating events in B-lineage acute lymphoblastic leukaemia (B-ALL); however, their clinical relevance across different age cohorts is unclear. We analysed the recurrent CNAs in 157 age-stratified B-ALL negative cases for recurrent rearrangements (B-NEG ALL), and their association with patients' clinico-biological features. We found that: (i) CDKN2A/RB1-deleted and EBF1-deleted adults had a shorter disease-free survival than those with wild-type, (ii) among the unfavourable markers, CDKN2A/RB1 deletions and K/NRAS mutations retained their impact in multivariate analysis, encouraging the evaluation of CDKN2A/RB1 deletions and RAS mutations in the diagnostic/prognostic workflow to refine ALL risk assessment...
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28401483/molecular-profiling-of-gene-copy-number-abnormalities-in-key-regulatory-genes-in-high-risk-b-lineage-acute-lymphoblastic-leukemia-frequency-and-their-association-with-clinicopathological-findings-in-indian-patients
#16
Prerana Bhandari, Firoz Ahmad, Bibhu Ranjan Das
Genes related to key cellular pathways are frequently altered in B cell ALL and are associated with poor survival especially in high-risk (HR) subgroups. We examined gene copy number abnormalities (CNA) in 101 Indian HR B cell ALL patients and their correlation with clinicopathological features by multiplex ligation-dependent probe amplification. Overall, CNA were detected in 59 (59%) cases, with 26, 10 and 23% of cases harboring 1, 2 or +3 CNA. CNA were more prevalent in BCR-ABL1 (60%), pediatric (64%) and high WCC (WBC count) (63%) patients...
May 2017: Medical Oncology
https://www.readbyqxmd.com/read/28369050/antagonism-of-b-cell-enhancer-networks-by-stat5-drives-leukemia-and-poor-patient-survival
#17
Casey D S Katerndahl, Lynn M Heltemes-Harris, Mark J L Willette, Christine M Henzler, Seth Frietze, Rendong Yang, Hilde Schjerven, Kevin A T Silverstein, Laura B Ramsey, Gregory Hubbard, Andrew D Wells, Roland P Kuiper, Blanca Scheijen, Frank N van Leeuwen, Markus Müschen, Steven M Kornblau, Michael A Farrar
The transcription factor STAT5 has a critical role in B cell acute lymphoblastic leukemia (B-ALL). How STAT5 mediates this effect is unclear. Here we found that activation of STAT5 worked together with defects in signaling components of the precursor to the B cell antigen receptor (pre-BCR), including defects in BLNK, BTK, PKCβ, NF-κB1 and IKAROS, to initiate B-ALL. STAT5 antagonized the transcription factors NF-κB and IKAROS by opposing regulation of shared target genes. Super-enhancers showed enrichment for STAT5 binding and were associated with an opposing network of transcription factors, including PAX5, EBF1, PU...
June 2017: Nature Immunology
https://www.readbyqxmd.com/read/28213137/foxo1-is-a-downstream-effector-of-isl1-in-direct-pathway-striatal-projection-neuron-development-within-the-embryonic-mouse-telencephalon
#18
R R Waclaw, L A Ehrman, P Merchan-Sala, V Kohli, D Nardini, K Campbell
Recent studies have shown that the LIM-homeodomain transcription factor Isl1 is required for the survival and differentiation of direct pathway striatonigral neurons during embryonic development. The downstream effectors of Isl1 in these processes are presently unknown. We show here that Foxo1, a transcription factor that has been implicated in cell survival, is expressed in striatal projection neurons (SPNs) that derive from the Isl1 lineage (i.e. direct pathway SPNs). Moreover, Isl1 conditional knockouts (cKOs) show a severe loss of Foxo1 expression at E15...
April 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28202519/correlates-of-prenatal-and-early-life-tobacco-smoke-exposure-and-frequency-of-common-gene-deletions-in-childhood-acute-lymphoblastic-leukemia
#19
Adam J de Smith, Maneet Kaur, Semira Gonseth, Alyson Endicott, Steve Selvin, Luoping Zhang, Ritu Roy, Xiaorong Shao, Helen M Hansen, Alice Y Kang, Kyle M Walsh, Gary V Dahl, Roberta McKean-Cowdin, Catherine Metayer, Joseph L Wiemels
Tobacco smoke exposure has been associated with risk of childhood acute lymphoblastic leukemia (ALL). Understanding the relationship between tobacco exposures and specific mutations may yield etiologic insights. We carried out a case-only analysis to explore whether prenatal and early-life tobacco smoke exposure influences the formation of leukemogenic genomic deletions. Somatic copy number of 8 genes frequently deleted in ALL (CDKN2A, ETV6, IKZF1, PAX5, RB1, BTG1, PAR1 region, and EBF1) was assessed in 559 pretreatment tumor samples from the California Childhood Leukemia Study...
April 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28193567/genomic-analysis-of-adult-b-all-identifies-potential-markers-of-shorter-survival
#20
MULTICENTER STUDY
Shiven Patel, Clinton C Mason, Martha J Glenn, Christian N Paxton, Sara T South, Melissa H Cessna, Julie Asch, Erin F Cobain, Dale L Bixby, Lauren B Smith, Shalini Reshmi, Julie M Gastier-Foster, Joshua D Schiffman, Rodney R Miles
B lymphoblastic leukemia (B-ALL) in adults has a higher risk of relapse and lower long-term survival than pediatric B-ALL, but data regarding genetic prognostic biomarkers are much more limited for adult patients. We identified 70 adult B-ALL patients from three institutions and performed genome-wide analysis via single nucleotide polymorphism (SNP) arrays on DNA isolated from their initial diagnostic sample and, when available, relapse bone marrow specimens to identify recurring copy number alterations (CNA)...
May 2017: Leukemia Research
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