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Se Ik Kim, Ji Won Lee, Nara Lee, Maria Lee, Hee Seung Kim, Hyun Hoon Chung, Jae-Weon Kim, Noh Hyun Park, Yong-Sang Song, Jeong-Sun Seo
BACKGROUND: Somatic amplifications of the LYL1 gene are relatively common occurrences in patients who develop uterine corpus endometrial carcinoma (UCEC) as opposed to other cancers. This study was undertaken to determine whether such genetic alterations affect survival outcomes of UCEC. METHODS: In 370 patients with UCEC, we analysed clinicopathologic characteristics and corresponding genomic data from The Cancer Genome Atlas database. Patients were stratified according to LYL1 gene status, grouped as amplification or non-amplification...
May 2, 2018: BMC Cancer
Isabelle Bergiers, Tallulah Andrews, Özge Vargel Bölükbaşı, Andreas Buness, Ewa Janosz, Natalia Lopez-Anguita, Kerstin Ganter, Kinga Kosim, Cemre Celen, Gülce Itır Perçin, Paul Collier, Bianka Baying, Vladimir Benes, Martin Hemberg, Christophe Lancrin
Recent advances in single-cell transcriptomics techniques have opened the door to the study of gene regulatory networks (GRNs) at the single-cell level. Here, we studied the GRNs controlling the emergence of hematopoietic stem and progenitor cells from mouse embryonic endothelium using a combination of single-cell transcriptome assays. We found that a heptad of transcription factors (Runx1, Gata2, Tal1, Fli1, Lyl1, Erg and Lmo2) is specifically co-expressed in an intermediate population expressing both endothelial and hematopoietic markers...
March 20, 2018: ELife
Eiichi Kimura, Takumi Abe, Kazumasa Murata, Toshiyuki Kimura, Yurika Otoki, Taiji Yoshida, Teruo Miyazawa, Kiyotaka Nakagawa
Tocopherol (Toc) and tocotrienol (T3) are abundant in rice bran. Geranylgeranyl reductase (GGR) is an essential enzyme for Toc production that catalyzes the reduction of geranylgeranyl pyrophosphate and geranylgeranyl-chlorophyll. However, we found that a rice mutant line with inactivated Os02g0744900 (OsGGR1/LYL1/OsChl P) gene produces Toc, suggesting that rice plants may carry another enzyme with GGR activity. Using an RNA-mediated interference technique, we demonstrated that the Os01g0265000 ("OsGGR2") gene product has GGR activity...
January 30, 2018: Scientific Reports
Bing Chen, Lu Jiang, Meng-Ling Zhong, Jian-Feng Li, Ben-Shang Li, Li-Jun Peng, Yu-Ting Dai, Bo-Wen Cui, Tian-Qi Yan, Wei-Na Zhang, Xiang-Qin Weng, Yin-Yin Xie, Jing Lu, Rui-Bao Ren, Su-Ning Chen, Jian-Da Hu, De-Pei Wu, Zhu Chen, Jing-Yan Tang, Jin-Yan Huang, Jian-Qing Mi, Sai-Juan Chen
T-cell acute lymphoblastic leukemia (T-ALL) is a clonal malignancy of immature T cells. Recently, the next-generation sequencing approach has allowed systematic identification of molecular features in pediatric T-ALL. Here, by performing RNA-sequencing and other genomewide analysis, we investigated the genomic landscape in 61 adult and 69 pediatric T-ALL cases. Thirty-six distinct gene fusion transcripts were identified, with SET-NUP214 being highly related to adult cases. Among 18 previously unknown fusions, ZBTB16-ABL1 , TRA-SALL2 , and involvement of NKX2-1 were recurrent events...
January 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
Qin Yan, Sun Hee Ahn, Felix Mba Medie, Batu K Sharma-Kuinkel, Lawrence P Park, William K Scott, Hitesh Deshmukh, Ephraim L Tsalik, Derek D Cyr, Christopher W Woods, Chen-Hsin Albert Yu, Carlton Adams, Robert Qi, Brenda Hansen, Vance G Fowler
We previously showed that chromosome 8 of A/J mice was associated with susceptibility to S. aureus infection. However, the specific genes responsible for this susceptibility are unknown. Chromosome substitution strain 8 (CSS8) mice, which have chromosome 8 from A/J but an otherwise C57BL/6J genome, were used to identify the genetic determinants of susceptibility to S. aureus on chromosome 8. Quantitative trait loci (QTL) mapping of S. aureus-infected N2 backcross mice (F1 [C8A] × C57BL/6J) identified a locus 83180780-88103009 (GRCm38/mm10) on A/J chromosome 8 that was linked to S...
2017: PloS One
Amit Mandoli, Abhishek A Singh, Koen H M Prange, Esther Tijchon, Marjolein Oerlemans, Rene Dirks, Menno Ter Huurne, Albertus T J Wierenga, Eva M Janssen-Megens, Kim Berentsen, Nilofar Sharifi, Bowon Kim, Filomena Matarese, Luan N Nguyen, Nina C Hubner, Nagesha A Rao, Emile van den Akker, Lucia Altucci, Edo Vellenga, Hendrik G Stunnenberg, Joost H A Martens
The t(8;21) acute myeloid leukemia (AML)-associated oncoprotein AML1-ETO disrupts normal hematopoietic differentiation. Here, we have investigated its effects on the transcriptome and epigenome in t(8,21) patient cells. AML1-ETO binding was found at promoter regions of active genes with high levels of histone acetylation but also at distal elements characterized by low acetylation levels and binding of the hematopoietic transcription factors LYL1 and LMO2. In contrast, ERG, FLI1, TAL1, and RUNX1 bind at all AML1-ETO-occupied regulatory regions, including those of the AML1-ETO gene itself, suggesting their involvement in regulating AML1-ETO expression levels...
November 15, 2016: Cell Reports
Sarah J Stein, Ethan A Mack, Kelly S Rome, Kostandin V Pajcini, Takuya Ohtani, Lanwei Xu, Yunlei Li, Jules P P Meijerink, Robert B Faryabi, Warren S Pear
Trib2 is highly expressed in human T cell acute lymphoblastic leukemia (T-ALL) and is a direct transcriptional target of the oncogenic drivers Notch and TAL1. In human TAL1-driven T-ALL cell lines, Trib2 is proposed to function as an important survival factor, but there is limited information about the role of Trib2 in primary T-ALL. In this study, we investigated the role of Trib2 in the initiation and maintenance of Notch-dependent T-ALL. Trib2 had no effect on the growth and survival of murine T-ALL cell lines in vitro when expression was blocked by shRNAs...
2016: PloS One
T Hoang, J A Lambert, R Martin
SCL, a transcription factor of the basic helix-loop-helix family, is a master regulator of hematopoiesis. Scl specifies lateral plate mesoderm to a hematopoietic fate and establishes boundaries by inhibiting the cardiac lineage. A combinatorial interaction between Scl and Vegfa/Flk1 sets in motion the first wave of primitive hematopoiesis. Subsequently, definitive hematopoietic stem cells (HSCs) emerge from the embryo proper via an endothelial-to-hematopoietic transition controlled by Runx1, acting with Scl and Gata2...
2016: Current Topics in Developmental Biology
Yuya Imamura, Miwa Haruta, Yusuke Tomita, Keiko Matsumura, Tokunori Ikeda, Akira Yuno, Masatoshi Hirayama, Hideki Nakayama, Hiroshi Mizuta, Yasuharu Nishimura, Satoru Senju
We previously reported a method to expand human monocytes through lentivirus-mediated introduction of cMYC and BMI1, and we named the monocyte-derived proliferating cells, CD14-ML. CD14-ML differentiated into functional DC (CD14-ML-DC) upon addition of IL-4, resulting in the generation of a large number of DC. One drawback of this method was the extensive donor-dependent variation in proliferation efficiency. In the current study, we found that introduction of BCL2 or LYL1 along with cMYC and BMI1 was beneficial...
2016: PloS One
A M Sotoca, K H M Prange, B Reijnders, A Mandoli, L N Nguyen, H G Stunnenberg, J H A Martens
The ETS transcription factor ERG has been implicated as a major regulator of both normal and aberrant hematopoiesis. In acute myeloid leukemias harboring t(16;21), ERG function is deregulated due to a fusion with FUS/TLS resulting in the expression of a FUS-ERG oncofusion protein. How this oncofusion protein deregulates the normal ERG transcription program is unclear. Here, we show that FUS-ERG acts in the context of a heptad of proteins (ERG, FLI1, GATA2, LYL1, LMO2, RUNX1 and TAL1) central to proper expression of genes involved in maintaining a stem cell hematopoietic phenotype...
April 14, 2016: Oncogene
Vaidas Dirse, Agne Bertasiute, Egle Gineikiene, Tadas Zvirblis, Ruta Dambrauskiene, Rolandas Gerbutavicius, Elona Juozaityte, Ligita Malciute, Kajsa Paulsson, Laimonas Griskevicius
Adult acute lymphoblastic leukemia (ALL) is characterized by a high frequency of abnormal karyotypes some of which are related to outcome. Single nucleotide polymorphism (SNP) array analysis provides a highly sensitive platform to detect large and small genomic aberrations. SNP array profiling data in adult ALL are limited and further systematic studies of this patient group are needed. We performed a population-based SNP array analysis of genomic aberrations and their influence on survival in 66 Lithuanian 18-65 year old ALL patients diagnosed between 2007 and 2013...
May 2015: Genes, Chromosomes & Cancer
Øystein Bruserud, Håkon Reikvam, Hanne Fredly, Jørn Skavland, Karen-Marie Hagen, Tuyen Thy van Hoang, Annette K Brenner, Amir Kadi, Audrey Astori, Bjørn Tore Gjertsen, Frederic Pendino
The CXXC5 gene encodes a transcriptional activator with a zinc-finger domain, and high expression in human acute myeloid leukemia (AML) cells is associated with adverse prognosis. We now characterized the biological context of CXXC5 expression in primary human AML cells. The global gene expression profile of AML cells derived from 48 consecutive patients was analyzed; cells with high and low CXXC5 expression then showed major differences with regard to extracellular communication and intracellular signaling...
February 20, 2015: Oncotarget
Bastien Gerby, Cedric S Tremblay, Mathieu Tremblay, Shanti Rojas-Sutterlin, Sabine Herblot, Josée Hébert, Guy Sauvageau, Sébastien Lemieux, Eric Lécuyer, Diogo F T Veiga, Trang Hoang
The molecular determinants that render specific populations of normal cells susceptible to oncogenic reprogramming into self-renewing cancer stem cells are poorly understood. Here, we exploit T-cell acute lymphoblastic leukemia (T-ALL) as a model to define the critical initiating events in this disease. First, thymocytes that are reprogrammed by the SCL and LMO1 oncogenic transcription factors into self-renewing pre-leukemic stem cells (pre-LSCs) remain non-malignant, as evidenced by their capacities to generate functional T cells...
December 2014: PLoS Genetics
Charnise Goodings, Rati Tripathi, Susan M Cleveland, Natalina Elliott, Yan Guo, Yu Shyr, Utpal P Davé
LIM domain only-2 (LMO2) overexpression in T cells induces leukemia but the molecular mechanism remains to be elucidated. In hematopoietic stem and progenitor cells, Lmo2 is part of a protein complex comprised of class II basic helix loop helix proteins, Tal1and Lyl1. The latter transcription factors heterodimerize with E2A proteins like E47 and Heb to bind E boxes. LMO2 and TAL1 or LYL1 cooperate to induce T-ALL in mouse models, and are concordantly expressed in human T-ALL. Furthermore, LMO2 cooperates with the loss of E2A suggesting that LMO2 functions by creating a deficiency of E2A...
January 2015: Leukemia Research
Aviya Goldshtein, Michael Berger
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes. Despite significant improvement in the treatment of T-ALL, approximately 20% of children and most adults succumb to resistant or relapsed disease. Transformation events occur during crucial steps of thymocyte development and have been related to the expression of certain oncogenes such as TAL2, TLX1, LYL1, LMO1, and NOTCH1. Mutations that lead to constitutive activation of NOTCH1 are most commonly found in human patients with T-ALL...
2014: Critical Reviews in Oncogenesis
Maxim Pimkin, Andrew V Kossenkov, Tejaswini Mishra, Christapher S Morrissey, Weisheng Wu, Cheryl A Keller, Gerd A Blobel, Dongwon Lee, Michael A Beer, Ross C Hardison, Mitchell J Weiss
Combinatorial actions of relatively few transcription factors control hematopoietic differentiation. To investigate this process in erythro-megakaryopoiesis, we correlated the genome-wide chromatin occupancy signatures of four master hematopoietic transcription factors (GATA1, GATA2, TAL1, and FLI1) and three diagnostic histone modification marks with the gene expression changes that occur during development of primary cultured megakaryocytes (MEG) and primary erythroblasts (ERY) from murine fetal liver hematopoietic stem/progenitor cells...
December 2014: Genome Research
Nadia El-Menshawy, Doaa Shahin, Hayam Fathi Ghazi
OBJECTIVE: Aberrant activation of transcription factor genes is the most frequent target of genetic alteration in lymphoid malignancies. The lymphoblastic leukemia-derived sequence 1 (LYL1) gene, which encodes a basic helix-loop helix, was first identified with human T-cell acute leukemia. Recent studies suggest its involvement in myeloid malignancies. We aimed to study the expression percent of oncogene LYL1 in primary and secondary high-risk myeloid leukemia and the impact on prognostic significance in those patients...
June 2014: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
Eun Ju Lee, Adeel Malik, Smritee Pokharel, Sarafraz Ahmad, Bilal Ahmad Mir, Kyung Hyun Cho, Jihoe Kim, Joon Chan Kong, Dong-Mok Lee, Ki Yong Chung, Sang Hoon Kim, Inho Choi
BACKGROUND: The expression of myogenic regulatory factors (MRFs) consisting of MyoD, Myf5, myogenin (MyoG) and MRF4 characterizes various phases of skeletal muscle development including myoblast proliferation, cell-cycle exit, cell fusion and the maturation of myotubes to form myofibers. Although it is well known that the function of MyoG cannot be compensated for other MRFs, the molecular mechanism by which MyoG controls muscle cell differentiation is still unclear. Therefore, in this study, RNA-Seq technology was applied to profile changes in gene expression in response to MyoG knock-down (MyoGkd) in primary bovine muscle satellite cells (MSCs)...
2014: PloS One
Christopher Veigaard, Anni Aggerholm, Henrik Hasle, Eigil Kjeldsen
Although childhood T-cell acute lymphoblastic leukemia (T-ALL) is a high-risk disease the outcome can vary considerably. The varying outcomes suggest that unrecognized factors may contribute to disease progression. We report on a 2-year-old T-ALL patient presenting with a very short history of constipation and extreme hyperleukocytosis (WBC 882×10(9)/L). In her leukemic cells we detected the very rare translocation t(7;19)(q35;p13) and LYL1 overexpression. Additionally, we detected submicroscopic deletions at 4q25, 7q33 and 10q23 by oligo-aCGH analysis...
2014: Leukemia Research Reports
Nelly Pirot, Hélène Delpech, Virginie Deleuze, Christiane Dohet, Monique Courtade-Saïdi, Céline Basset-Léobon, Elias Chalhoub, Danièle Mathieu, Valérie Pinet
Maturation of newly formed vessels is a multistep phenomenon during which functional endothelial barriers are established. Disruption of vessel integrity is an important feature in many physiological and pathological processes. We previously reported that lymphoblastic leukemia-derived sequence 1 (LYL1) is required for the late stages of postnatal angiogenesis to limit the formation of new blood vessels, notably by regulating the activity of the small GTPase Rap1. In this study, we show that LYL1 is also required during the formation of the mature endothelial barrier in the lungs of adult mice...
April 15, 2014: American Journal of Physiology. Lung Cellular and Molecular Physiology
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