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https://www.readbyqxmd.com/read/27913602/clonal-conversion-of-b-lymphoid-leukemia-reveals-cross-lineage-transfer-of-malignant-states
#1
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...
December 2, 2016: Genes & Development
https://www.readbyqxmd.com/read/27911806/permissive-roles-of-cytokines-interleukin-7-and-flt3-ligand-in-mouse-b-cell-lineage-commitment
#2
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...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27889898/the-transcription-factors-ebf1-and-ebf2-are-positive-regulators-of-myelination-in-schwann-cells
#3
Diego Moruzzo, Lucilla Nobbio, Bruno Sterlini, G Giacomo Consalez, Fabio Benfenati, Angelo Schenone, Anna Corradi
Myelin formation by Schwann cells is tightly controlled by multiple pathways and regulatory molecules. The Ebf2 gene, belonging to the Ebf family of transcription factors regulating cell development and differentiation, is expressed in Schwann cells, and Ebf2 knockout mice show peripheral nerve defects. We also found that Ebf1 is expressed in Schwann cells. To investigate Ebf function in myelination, we silenced Ebf genes in myelinating dorsal root ganglia cultures. Combined downregulation of Ebf genes leads to a severe impairment of myelin formation that is completely rescued by their specific overexpression, suggesting that the expression level of Ebf genes strongly influences axon myelination...
November 26, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27889482/the-red-light-receptor-phytochrome-b-directly-enhances-substrate-e3-ligase-interactions-to-attenuate-ethylene-responses
#4
Hui Shi, Xing Shen, Renlu Liu, Chang Xue, Ning Wei, Xing Wang Deng, Shangwei Zhong
Plants germinating under subterranean darkness assume skotomorphogenesis, a developmental program strengthened by ethylene in response to mechanical pressure of soil. Upon reaching the surface, light triggers a dramatic developmental transition termed de-etiolation that requires immediate termination of ethylene responses. Here, we report that light activation of photoreceptor phyB results in rapid degradation of EIN3, the master transcription factor in the ethylene signaling pathway. As a result, light rapidly and efficiently represses ethylene actions...
November 16, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27876533/multiple-single-nucleotide-polymorphisms-in-the-first-intron-of-the-il2ra-gene-affect-transcription-factor-binding-and-enhancer-activity
#5
Anton M Schwartz, Denis E Demin, Ilya E Vorontsov, Artem S Kasyanov, Lidia V Putlyaeva, Karina A Tatosyan, Ivan V Kulakovskiy, Dmitry V Kuprash
IL2RA gene encodes the alpha subunit of a high-affinity receptor for interleukin-2 which is expressed by several distinct populations of lymphocytes involved in autoimmune processes. A large number of polymorphic alleles of the IL2RA locus are associated with the development of various autoimmune diseases. With bioinformatics analysis we the dissected the first intron of the IL2RA gene and selected several single nucleotide polymorphisms (SNPs) that may influence the regulation of the IL2RA gene in cell types relevant to autoimmune pathology...
November 19, 2016: Gene
https://www.readbyqxmd.com/read/27855558/diagnostic-evaluation-of-rna-sequencing-for-the-detection-of-genetic-abnormalities-associated-with-ph-like-acute-lymphoblastic-leukemia-all
#6
Kai Lee Yap, Larissa V Furtado, Kazuma Kiyotani, Emily Curran, Wendy Stock, Jennifer L McNeer, Sabah Kadri, Jeremy P Segal, Yusuke Nakamura, Michelle M Le Beau, Sandeep Gurbuxani, Gordana Raca
Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) is a molecular subtype of high-risk B-cell ALL characterized by formation of abnormal gene fusions involving tyrosine kinase (TK) and cytokine receptor genes and activation of TK signaling. Because of the diversity of associated genetic changes, the detection of Ph-like ALL cases currently requires multiple cytogenetic and molecular assays; thus, our goal was to develop a consolidated workflow for detecting genetic abnormalities in Ph-like ALL. We found that total and targeted RNA sequencing (RNAseq)-based approach allowed the detection of abnormal fusion transcripts (EBF1-PDGFRB, P2RY8-CRLF2, RCSD1-ABL1, and RCSD1-ABL2)...
November 17, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27822221/activation-of-hls1-by-mechanical-stress-via-ethylene-stabilized-ein3-is-crucial-for-seedling-soil-emergence
#7
Xing Shen, Yanli Li, Ying Pan, Shangwei Zhong
The seeds of terrestrial flowering plants often start their life cycle in subterranean darkness. To protect the fragile apical meristematic tissues and cotyledons from mechanical injuries during soil penetration, dicotyledonous seedlings form an elegant apical hook at the top of the hypocotyl. The apical hook has been considered as an adaption structure to the subterranean environment. However, the role of the apical hook in seedling emergence and the molecular mechanism of apical hook formation under real-life conditions remain highly speculative...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27816938/genome-wide-association-study-of-parental-life-span
#8
Toshiko Tanaka, Ambarish Dutta, Luke C Pilling, Luting Xue, Kathryn L Lunetta, Joanne M Murabito, Stefania Bandinelli, Robert Wallace, David Melzer, Luigi Ferrucci
BACKGROUND: Having longer lived parents has been shown to be an important predictor of health trajectories and life span. As such, parental life span is an important phenotype that may uncover genes that affect longevity. METHODS: A genome-wide association study of parental life span in participants of European and African ancestry from the Health and Retirement Study was conducted. RESULTS: A genome-wide significant association was observed for rs35715456 (log10BF = 6...
November 5, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/27807034/interaction-of-ccr4-not-with-ebf1-regulates-gene-specific-transcription-and-mrna-stability-in-b-lymphopoiesis
#9
Cheng-Yuan Yang, Senthilkumar Ramamoorthy, Sören Boller, Marc Rosenbaum, Alfonso Rodriguez Gil, Gerhard Mittler, Yumiko Imai, Keiji Kuba, Rudolf Grosschedl
Transcription factor EBF1 (early B-cell factor 1) regulates early B-cell differentiation by poising or activating lineage-specific genes and repressing genes associated with alternative cell fates. To identify proteins that regulate the diverse functions of EBF1, we used SILAC (stable isotope labeling by amino acids in cell culture)-based mass spectrometry of proteins associated with endogenous EBF1 in pro-B cells. This analysis identified most components of the multifunctional CCR4-NOT complex, which regulates transcription and mRNA degradation...
October 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27744667/replication-of-early-b-cell-factor-1-ebf1-gene-by-psychosocial-stress-interaction-effects-on-central-adiposity-in-a-korean-population
#10
Hyun-Jin Kim, Jin-Young Min, Kyoung-Bok Min
OBJECTIVES: Central obesity plays a major role in the development of many chronic diseases, including cardiovascular disease and cancer. Chronic stress may be involved in the pathophysiology of central obesity. Although several large-scale genome-wide association studies have reported susceptibility genes for central adiposity, the effects of interactions between genes and psychosocial stress on central adiposity have rarely been examined. A recent study focusing on Caucasians discovered the novel gene early B-cell factor 1 (EBF1), which was associated with central obesity-related traits via interactions with stress levels...
September 2016: Journal of Preventive Medicine and Public Health, Yebang Ŭihakhoe Chi
https://www.readbyqxmd.com/read/27664237/superenhancer-reprogramming-drives-a-b-cell-epithelial-transition-and-high-risk-leukemia
#11
Yeguang Hu, Zhihong Zhang, Mariko Kashiwagi, Toshimi Yoshida, Ila Joshi, Nilamani Jena, Rajesh Somasundaram, Akinola Olumide Emmanuel, Mikael Sigvardsson, Julien Fitamant, Nabeel El-Bardeesy, Fotini Gounari, Richard A Van Etten, Katia Georgopoulos
IKAROS is required for the differentiation of highly proliferative pre-B-cell precursors, and loss of IKAROS function indicates poor prognosis in precursor B-cell acute lymphoblastic leukemia (B-ALL). Here we show that IKAROS regulates this developmental stage by positive and negative regulation of superenhancers with distinct lineage affiliations. IKAROS defines superenhancers at pre-B-cell differentiation genes together with B-cell master regulators such as PAX5, EBF1, and IRF4 but is required for a highly permissive chromatin environment, a function that cannot be compensated for by the other transcription factors...
September 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/27539385/gene-expression-analysis-of-developing-cell-groups-in-the-pretectal-region-of-xenopus-laevis
#12
Ruth Morona, José Luis Eduardo Ferran, Luis Puelles, Agustín González
Our previous analysis of progenitor domains in the pretectum of Xenopus revealed three molecularly distinct anteroposterior subdivisions identified as precommissural (PcP), juxtacommissural (JcP), and commissural (CoP) histogenetic domains (Morona et al. [2011] J Comp Neurol 519:1024-1050). Here we analyzed at later developmental stages the nuclei derived from these areas, attending to their gene expression patterns and histogenesis. Transcription-factor gene markers were used to selectively map derivatives of each domain: Pax7 and Pax6 (CoP); Foxp1 and Six3 (JcP); and Xiro1, VGlut2, Ebf1, and Ebf3 (PcP)...
August 19, 2016: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/27460500/cd19-car-immune-pressure-induces-b-precursor-acute-lymphoblastic-leukaemia-lineage-switch-exposing-inherent-leukaemic-plasticity
#13
Elad Jacoby, Sang M Nguyen, Thomas J Fountaine, Kathryn Welp, Berkley Gryder, Haiying Qin, Yinmeng Yang, Christopher D Chien, Alix E Seif, Haiyan Lei, Young K Song, Javed Khan, Daniel W Lee, Crystal L Mackall, Rebecca A Gardner, Michael C Jensen, Jack F Shern, Terry J Fry
Adoptive immunotherapy using chimeric antigen receptor (CAR) expressing T cells targeting the CD19 B lineage receptor has demonstrated marked success in relapsed pre-B-cell acute lymphoblastic leukaemia (ALL). Persisting CAR-T cells generate sustained pressure against CD19 that may drive unique mechanisms of resistance. Pre-B ALL originates from a committed pre-B cell or an earlier progenitor, with potential to reprogram into other hematopoietic lineages. Here we report changes in lineage markers including myeloid conversion in patients following CD19 CAR therapy...
2016: Nature Communications
https://www.readbyqxmd.com/read/27424222/early-b-cell-factor-1-ebf1-is-critical-for-transcriptional-control-of-slamf1-gene-in-human-b-cells
#14
Anton M Schwartz, Lidia V Putlyaeva, Milica Covich, Anna V Klepikova, Kseniya A Akulich, Ilya E Vorontsov, Kirill V Korneev, Sergey E Dmitriev, Oleg L Polanovsky, Svetlana P Sidorenko, Ivan V Kulakovskiy, Dmitry V Kuprash
Signaling lymphocytic activation molecule family member 1 (SLAMF1)/CD150 is a co-stimulatory receptor expressed on a variety of hematopoietic cells, in particular on mature lymphocytes activated by specific antigen, costimulation and cytokines. Changes in CD150 expression level have been reported in association with autoimmunity and with B-cell chronic lymphocytic leukemia. We characterized the core promoter for SLAMF1 gene in human B-cell lines and explored binding sites for a number of transcription factors involved in B cell differentiation and activation...
October 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27339065/gene-copy-number-alteration-profile-and-its-clinical-correlation-in-b-cell-acute-lymphoblastic-leukemia
#15
Sanjeev Kumar Gupta, Sameer Bakhshi, Lalit Kumar, Vineet Kumar Kamal, Rajive Kumar
The genes related to B-cell development are frequently altered in B-cell acute lymphoblastic leukemia (B-ALL). One hundred sixty-two newly diagnosed B-ALL cases, median age 8.5 years (2 months-67 years), were prospectively analyzed for copy number alterations (CNAs) in CDKN2A/B, IKZF1, PAX5, RB1, ETV6, BTG1, EBF1, and pseudoautosomal region genes (CRLF2, CSF2RA, IL3RA) using multiplex ligation-dependent probe amplification. The CNAs were detected in 114 (70.4%) cases; most commonly affected genes being CDKN2A/B-55 (34%), PAX5-51 (31...
June 24, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27210878/-ph-like-b-cell-precursor-acute-lymphoblastic-leukemia-with-ebf1-pdgfrb-fusion-gene-a-case-report-and-literatures-review
#16
J J Zheng, S N Chen, A N Sun, D P Wu
No abstract text is available yet for this article.
May 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/27166193/repression-of-tcf3-e2a-contributes-to-hodgkin-lymphomagenesis
#17
Hanfeng Guan, Linka Xie, Thomas Wirth, Alexey Ushmorov
Although Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) derived from germinal or post germinal B cells, they have lost the B cell phenotype in the process of lymphomagenesis. The phenomenon can be at least partially explained by repression of B-cell-specific transcription factors including TCF3, early B-cell factor 1 (EBF1), SPI1/PU.1, and FOXO1, which are down-regulated by genetic and epigenetic mechanisms. The unique phenotype has been suspected to be advantageous for survival of HRS cells...
June 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27142338/prostate-tumor-dna-methylation-is-associated-with-cigarette-smoking-and-adverse-prostate-cancer-outcomes
#18
Irene M Shui, Chao-Jen Wong, Shanshan Zhao, Suzanne Kolb, Ericka M Ebot, Milan S Geybels, Rohina Rubicz, Jonathan L Wright, Daniel W Lin, Brandy Klotzle, Marina Bibikova, Jian-Bing Fan, Elaine A Ostrander, Ziding Feng, Janet L Stanford
BACKGROUND: DNA methylation has been hypothesized as a mechanism for explaining the association between smoking and adverse prostate cancer (PCa) outcomes. This study was aimed at assessing whether smoking is associated with prostate tumor DNA methylation and whether these alterations may explain in part the association of smoking with PCa recurrence and mortality. METHODS: A total of 523 men had radical prostatectomy as their primary treatment, detailed smoking history data, long-term follow-up for PCa outcomes, and tumor tissue profiled for DNA methylation...
July 15, 2016: Cancer
https://www.readbyqxmd.com/read/26982363/pioneering-activity-of-the-c-terminal-domain-of-ebf1-shapes-the-chromatin-landscape-for-b-cell-programming
#19
Sören Boller, Senthilkumar Ramamoorthy, Duygu Akbas, Robert Nechanitzky, Lukas Burger, Rabih Murr, Dirk Schübeler, Rudolf Grosschedl
Lymphopoiesis requires the activation of lineage-specific genes embedded in naive, inaccessible chromatin or in primed, accessible chromatin. The mechanisms responsible for de novo gain of chromatin accessibility, known as "pioneer" function, remain poorly defined. Here, we showed that the EBF1 C-terminal domain (CTD) is required for the regulation of a specific gene set involved in B cell fate decision and differentiation, independently of activation and repression functions. Using genome-wide analysis of DNaseI hypersensitivity and DNA methylation in multipotent Ebf1(-/-) progenitors and derivative EBF1wt- or EBF1ΔC-expressing cells, we found that the CTD promoted chromatin accessibility and DNA demethylation in previously naive chromatin...
March 15, 2016: Immunity
https://www.readbyqxmd.com/read/26982358/a-pioneer-s-tail
#20
COMMENT
Ranjan Sen
In this issue of Immunity, Boller et al. (2016) show that a C-terminal domain of EBF1 is required for chromatin binding and induction of DNase I hypersensitive sites. These properties mark EBF1 as a pioneer factor in B cell development and demonstrate a role for non-DNA binding domains in this process.
March 15, 2016: Immunity
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