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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
#1
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
#2
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
#3
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...
April 3, 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
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/28192372/rna-binding-protein-pspc1-promotes-the-differentiation-dependent-nuclear-export-of-adipocyte-rnas
#7
Jiexin Wang, Prashant Rajbhandari, Andrey Damianov, Areum Han, Tamer Sallam, Hironori Waki, Claudio J Villanueva, Stephen D Lee, Ronni Nielsen, Susanne Mandrup, Karen Reue, Stephen G Young, Julian Whitelegge, Enrique Saez, Douglas L Black, Peter Tontonoz
A highly orchestrated gene expression program establishes the properties that define mature adipocytes, but the contribution of posttranscriptional factors to the adipocyte phenotype is poorly understood. Here we have shown that the RNA-binding protein PSPC1, a component of the paraspeckle complex, promotes adipogenesis in vitro and is important for mature adipocyte function in vivo. Cross-linking and immunoprecipitation followed by RNA sequencing revealed that PSPC1 binds to intronic and 3'-untranslated regions of a number of adipocyte RNAs, including the RNA encoding the transcriptional regulator EBF1...
March 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28183271/association-in-a-chinese-population-of-a-genetic-variation-in-the-early-b-cell-factor-1-gene-with-coronary-artery-disease
#8
Yafei Li, Zhiyong Xie, Lei Chen, Jianjun Yan, Yao Ma, Liansheng Wang, Zhong Chen
BACKGROUND: Early B-cell factor 1 (EBF1) is a transcription factor expressed primarily during early B cell development. Previous studies have shown EBF1 regulates blood glucose and lipid metabolism in mice with diabetes and central adiposity. Recently, a genetic variation (rs36071027) located in an EBF1 gene intron was associated with carotid artery intima-media thickness. However, whether this polymorphism is actually linked with coronary artery disease (CAD) and its severity remains unclear...
February 10, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28137879/differentiation-of-human-telencephalic-progenitor-cells-into-msns-by-inducible-expression-of-gsx2-and-ebf1
#9
Andrea Faedo, Angela Laporta, Alice Segnali, Maura Galimberti, Dario Besusso, Elisabetta Cesana, Sara Belloli, Rosa Maria Moresco, Marta Tropiano, Elisa Fucà, Stefan Wild, Andreas Bosio, Alessandro E Vercelli, Gerardo Biella, Elena Cattaneo
Medium spiny neurons (MSNs) are a key population in the basal ganglia network, and their degeneration causes a severe neurodegenerative disorder, Huntington's disease. Understanding how ventral neuroepithelial progenitors differentiate into MSNs is critical for regenerative medicine to develop specific differentiation protocols using human pluripotent stem cells. Studies performed in murine models have identified some transcriptional determinants, including GS Homeobox 2 (Gsx2) and Early B-cell factor 1 (Ebf1)...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28105631/association-of-genetic-variation-with-blood-pressure-traits-among-east-africans
#10
J Kayima, J Liang, Y Natanzon, J Nankabirwa, I Ssinabulya, J Nakibuuka, A Katamba, H Mayanja-Kizza, A Miron, C Li, X Zhu
INTRODUCTION: Genetic variation may play explain some of the disparity in prevalence and control of hypertension across Sub-Saharan Africa. However, there have been very few studies to characterize genetic variation of blood pressure traits. AIM: To determine whether a set of blood pressure-associated genetic loci can be replicated among samples East African samples. METHODS: Twenty-seven blood pressures (BP)-related single nucleotide polymorphisms (SNPs) were genotyped among 2881 samples from participants in the Medical Education Partnership Initiative for Cardiovascular Disease (MEPI-CVD) survey...
January 20, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28049421/placental-transcriptome-co-expression-analysis-reveals-conserved-regulatory-programs-across-gestation
#11
Sam Buckberry, Tina Bianco-Miotto, Stephen J Bent, Vicki Clifton, Cheryl Shoubridge, Kartik Shankar, Claire T Roberts
BACKGROUND: Mammalian development in utero is absolutely dependent on proper placental development, which is ultimately regulated by the placental genome. The regulation of the placental genome can be directly studied by exploring the underlying organisation of the placental transcriptome through a systematic analysis of gene-wise co-expression relationships. RESULTS: In this study, we performed a comprehensive analysis of human placental co-expression using RNA sequencing and intergrated multiple transcriptome datasets spanning human gestation...
January 3, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28045622/use-of-minimal-residual-disease-assessment-to-redefine-induction-failure-in-pediatric-acute-lymphoblastic-leukemia
#12
David O'Connor, Anthony V Moorman, Rachel Wade, Jeremy Hancock, Ronald M R Tan, Jack Bartram, John Moppett, Claire Schwab, Katharine Patrick, Christine J Harrison, Rachael Hough, Nick Goulden, Ajay Vora, Sujith Samarasinghe
Purpose Our aim was to determine the role of end-of-induction (EOI) minimal residual disease (MRD) assessment in the identification and stratification of induction failure in patients with pediatric acute lymphoblastic leukemia (ALL) and to identify genetic abnormalities that drive disease in these patients. Patients and Methods Analysis included 3,113 patients who were treated in the Medical Research Council UKALL2003 multicenter randomized trial (NCT00222612) between 2003 and 2011. MRD was measured by using standardized real-time quantitative PCR...
February 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28010895/platelet-derived-growth-factor-receptors-pdgfrs-fusion-genes-involvement-in-hematological-malignancies
#13
REVIEW
Kwaku Appiah-Kubi, Ting Lan, Ying Wang, Hai Qian, Min Wu, Xiaoyuan Yao, Yan Wu, Yongchang Chen
PURPOSE: To investigate oncogenic platelet-derived growth factor receptor(PDGFR) fusion genes involvement in hematological malignancies, the advances in the PDGFR fusion genes diagnosis and development of PDGFR fusions inhibitors. METHODS: Literature search was done using terms "PDGFR and Fusion" or "PDGFR and Myeloid neoplasm" or 'PDGFR and Lymphoid neoplasm' or "PDGFR Fusion Diagnosis" or "PDGFR Fusion Targets" in databases including PubMed, ASCO.org, and Medscape...
January 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27983964/functional-consequences-of-i56ii-dlx-enhancer-deletion-in-the-developing-mouse-forebrain
#14
S Fazel Darbandi, L Poitras, S Monis, S Lindtner, M Yu, G Hatch, J L Rubenstein, M Ekker
Dlx homeobox genes encode a group of transcription factors that play an essential role during developmental processes including maintaining the differentiation, proliferation and migration of GABAergic interneurons. The Dlx1/2 and Dlx5/6 genes are expressed in the forebrain and are arranged in convergently transcribed bigene clusters, with I12a/I12b and I56i/I56ii cis-regulatory elements (CREs) located in the intergenic region of each cluster respectively. We have characterized the phenotypic consequences of deleting I56ii on forebrain development and spatial patterning of corridor cells that are involved in guiding thalamocortical projections...
October 27, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27979924/tumor-suppressors-btg1-and-ikzf1-cooperate-during-mouse-leukemia-development-and-increase-relapse-risk-in-b-cell-precursor-acute-lymphoblastic-leukemia-patients
#15
Blanca Scheijen, Judith M Boer, Rene' Marke, Esther Tijchon, Dorette van Ingen Schenau, Esme' Waanders, Liesbeth van Emst, Laurens T van der Meer, Rob Pieters, Gabriele Escherich, Martin A Horstmann, Edwin Sonneveld, Nicola Venn, Rosemary Sutton, Luciano Dalla-Pozza, Roland P Kuiper, Peter M Hoogerbrugge, Monique L den Boer, Frank N van Leeuwen
Deletions and mutations affecting lymphoid transcription factor IKZF1 (IKAROS) are associated with an increased relapse risk and poor outcome in B-cell precursor acute lymphoblastic leukemia. However, additional genetic events may either enhance or negate the effects of IKZF1 deletions on prognosis. In a large discovery cohort of 533 childhood B-cell precursor acute lymphoblastic leukemia patients, we observed that single copy losses of BTG1 were significantly enriched in IKZF1-deleted B-cell precursor acute lymphoblastic leukemia (P=0...
December 15, 2016: Haematologica
https://www.readbyqxmd.com/read/27924221/targeting-mll1-h3k4-methyltransferase-activity-to-guide-cardiac-lineage-specific-reprogramming-of-fibroblasts
#16
Liu Liu, Ienglam Lei, Hacer Karatas, Yangbing Li, Li Wang, Leonid Gnatovskiy, Yali Dou, Shaomeng Wang, Li Qian, Zhong Wang
Generation of induced cardiomyocytes (iCMs) directly from fibroblasts offers a great opportunity for cardiac disease modeling and cardiac regeneration. A major challenge of iCM generation is the low conversion rate. To address this issue, we attempted to identify small molecules that could potentiate the reprogramming ability towards cardiac fate by removing inhibitory roadblocks. Using mouse embryonic fibroblasts as the starting cell source, we first screened 47 cardiac development related epigenetic and transcription factors, and identified an unexpected role of H3K4 methyltransferase Mll1 and related factor Men1 in inhibiting iCM reprogramming...
2016: Cell Discovery
https://www.readbyqxmd.com/read/27923118/cutting-out-the-middle-man-in-light-hormone-interactions
#17
Anna N Stepanova, Jose M Alonso
In this issue of Developmental Cell, Shi et al. (2016a) show that red-light-activated phytochrome B interacts with transcriptional regulators of ethylene signaling, EIN3/EIL1, triggering their degradation by bringing the F-box proteins EBF1 and 2 to the complex. These findings provide a paradigm for crosstalk between light and hormone signaling pathways.
December 5, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27918534/multiethnic-genome-wide-meta-analysis-of-ectopic-fat-depots-identifies-loci-associated-with-adipocyte-development-and-differentiation
#18
Audrey Y Chu, Xuan Deng, Virginia A Fisher, Alexander Drong, Yang Zhang, Mary F Feitosa, Ching-Ti Liu, Olivia Weeks, Audrey C Choh, Qing Duan, Thomas D Dyer, John D Eicher, Xiuqing Guo, Nancy L Heard-Costa, Tim Kacprowski, Jack W Kent, Leslie A Lange, Xinggang Liu, Kurt Lohman, Lingyi Lu, Anubha Mahajan, Jeffrey R O'Connell, Ankita Parihar, Juan M Peralta, Albert V Smith, Yi Zhang, Georg Homuth, Ahmed H Kissebah, Joel Kullberg, René Laqua, Lenore J Launer, Matthias Nauck, Michael Olivier, Patricia A Peyser, James G Terry, Mary K Wojczynski, Jie Yao, Lawrence F Bielak, John Blangero, Ingrid B Borecki, Donald W Bowden, John Jeffrey Carr, Stefan A Czerwinski, Jingzhong Ding, Nele Friedrich, Vilmunder Gudnason, Tamara B Harris, Erik Ingelsson, Andrew D Johnson, Sharon L R Kardia, Carl D Langefeld, Lars Lind, Yongmei Liu, Braxton D Mitchell, Andrew P Morris, Thomas H Mosley, Jerome I Rotter, Alan R Shuldiner, Bradford Towne, Henry Völzke, Henri Wallaschofski, James G Wilson, Matthew Allison, Cecilia M Lindgren, Wolfram Goessling, L Adrienne Cupples, Matthew L Steinhauser, Caroline S Fox
Variation in body fat distribution contributes to the metabolic sequelae of obesity. The genetic determinants of body fat distribution are poorly understood. The goal of this study was to gain new insights into the underlying genetics of body fat distribution by conducting sample-size-weighted fixed-effects genome-wide association meta-analyses in up to 9,594 women and 8,738 men of European, African, Hispanic and Chinese ancestry, with and without sex stratification, for six traits associated with ectopic fat (hereinafter referred to as ectopic-fat traits)...
January 2017: Nature Genetics
https://www.readbyqxmd.com/read/27913602/clonal-conversion-of-b-lymphoid-leukemia-reveals-cross-lineage-transfer-of-malignant-states
#19
Rajesh Somasundaram, Josefine Åhsberg, Kazuki Okuyama, Jonas Ungerbäck, Henrik Lilljebjörn, Thoas Fioretos, Tobias Strid, Mikael Sigvardsson
Even though leukemia is considered to be confined to one specific hematopoietic cell type, cases of acute leukemia of ambiguous lineage and patients relapsing in phenotypically altered disease suggest that a malignant state may be transferred between lineages. Because B-cell leukemia is associated with mutations in transcription factors of importance for stable preservation of lineage identity, we here investigated the potential lineage plasticity of leukemic cells. We report that primary pro-B leukemia cells from mice carrying heterozygous mutations in either or both the Pax5 and Ebf1 genes, commonly mutated in human leukemia, can be converted into T lineage leukemia cells...
November 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27911806/permissive-roles-of-cytokines-interleukin-7-and-flt3-ligand-in-mouse-b-cell-lineage-commitment
#20
Lilly von Muenchow, Llucia Alberti-Servera, Fabian Klein, Giuseppina Capoferri, Daniela Finke, Rhodri Ceredig, Antonius Rolink, Panagiotis Tsapogas
Hematopoietic cells are continuously generated throughout life from hematopoietic stem cells, thus making hematopoiesis a favorable system to study developmental cell lineage commitment. The main factors incorporating environmental signals to developing hematopoietic cells are cytokines, which regulate commitment of hematopoietic progenitors to the different blood lineages by acting either in an instructive or a permissive manner. Fms-like tyrosine kinase-3 (Flt3) ligand (FL) and Interleukin-7 (IL-7) are cytokines pivotal for B-cell development, as manifested by the severely compromised B-cell development in their absence...
December 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
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