DOCSLIB.ORG

Leukaemia Section

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Atlas of Genetics and Cytogenetics in Oncology and Haematology INIST -CNRS OPEN ACCESS JOURNAL Leukaemia Section Short Communication t(12;12)(p13;q13) ETV6/BAZ2A Jean-Loup Huret Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France (JLH) Published in Atlas Database: March 2013 Online updated version : http://AtlasGeneticsOncology.org/Anomalies/t1212p13q13ID1452.html DOI: 10.4267/2042/51429 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2013 Atlas of Genetics and Cytogenetics in Oncology and Haematology Clinics and pathology Cytogenetics Disease Cytogenetics morphological Acute leukemias In the case where ETV6/BAZ2A rearrangement was ascertained, the rearrangement between 12p13 and Clinics 12q13 was cryptic (Panagopoulos et al., 2006). The Out of 5 cases herein taken into account, 3 cases other ALL case also had a trisomy 16 and a trisomy 21. presented with a rearranged ETV6 gene, and only one The t(12;12)(p13;q13) was an additional anomaly to a of these cases was identified to carry an ETV6/BAZ2A t(11;19)(q23;p13.1) in the treatment related AML-M2 hybrid gene. This case was a 3-year-old girl with a pre- case. B acute lymphoblastic leukaemia (CD10+ ALL). She The apparently de novo AML-M2 case have had a achieved complete remission (CR), and was remaining del(7q) prior to the t(12;12). in CR 18 months after diagnosis (Panagopoulos et al., The M6-AML case had a del(5q), a del(20q) and a 2006). complex karyotype. The 2 other ETV6+ cases were acute myeloid leukemia (AML) cases: a 77-year-old male patient with AML- Genes involved and proteins M2. Complete remission was achieved; he relapsed and died of sepsis (Saitoh et al., 2002); and a 46-year-old ETV6 female patient with treatment related AML-M2, Location developping years after treatment for breast cancer; the 12p13.2 patient has been in continuous relapse for the last 4 Protein months after onset of AML (Manola et al., 2008). ETV6 is a transcriptional repressor belonging to the The 2 last cases were: a 4-years-old boy with ALL; the ETS family. ETV6 displays a HLH domain (also patient was alive 27 months after diagnosis (Heerema referred to as the pointed (PNT) or sterile alpha motif et al., 1985); and a 62-years-old female patient with (SAM) domain), responsible for hetero- and AML-M6 with a 2 months survival (Mazzella et al., homodimerization, a central domain involved in the 1998). recruitment of a repression complex including NCOR2 Altogether, this makes 2 pediatric ALL cases, and 3 and SIN3, and an ETS domain, responsible for adult AML cases, with perhaps different prognoses sequence specific DNA-binding to DNA-responsive between the two categories. Excluded here is a case of elements. refractory anemia with excess blasts with HMGA2 Repression involves the recruitment of co-repressor involvement (Odero et al., 2005), although the 4 above complexes and HDACs or the recruitment of mentionned cases where BAZ2A was not studied may L3MBTL-containing polycomb group-complexes that also have had a HMGA2 rearrangement. facilitate repression by chromatin remodeling. ETV6 Atlas Genet Cytogenet Oncol Haematol. 2013; 17(9) 640 t(12;12)(p13;q13) ETV6/BAZ2A Huret JL binds to nuclear receptors RARA and RXRA and represses gene activation. ETV6 is as a selective and References essential regulator of stem cells, important in vitelline Heerema NA, Palmer CG, Baehner RL. Karyotypic and clinical angiogenesis and in bone marrow hematopoiesis. ETV6 findings in a consecutive series of children with acute lymphocytic leukemia. Cancer Genet Cytogenet. 1985 expands erythroid precursors and stimulates Jun;17(2):165-79 hemoglobin synthesis (Knezevich, 2005; Eguchi- Ishimae et al., 2009; Meester-Smoor et al., 2011). Mazzella FM, Kowal-Vern A, Shrit MA, Wibowo AL, Rector JT, Cotelingam JD, Collier J, Mikhael A, Cualing H, Schumacher BAZ2A HR. Acute erythroleukemia: evaluation of 48 cases with reference to classification, cell proliferation, cytogenetics, and Location prognosis. Am J Clin Pathol. 1998 Nov;110(5):590-8 12q13.3 Saitoh T, Nakamura T, Inoue M, Hatta Y, Yamazaki T, Protein Takeuchi J, Sawada U, Horie T. Different clones of BAZ2A comprises from N-term to C-term a MBD t(1;12)/t(12;12) involving the ETV6 gene in a case of acute (methyl-CpG-binding) domain, 2 AT hooks, a DDT myeloid leukemia. Cancer Genet Cytogenet. 2002 Sep;137(2):138-41 (DNA binding homeobox and different transcription factors), 2 AT hooks again, a PHD-type zinc finger, Odero MD, Grand FH, Iqbal S, Ross F, Roman JP, Vizmanos and a bromo domain. The bromo domain and the PHD- JL, Andrieux J, Laï JL, Calasanz MJ, Cross NC. Disruption and aberrant expression of HMGA2 as a consequence of diverse type zinc finger recognize and bind histone H4. These 2 chromosomal translocations in myeloid malignancies. domains play a central role in the recruitment of Leukemia. 2005 Feb;19(2):245-52 chromatin silencing proteins such as DNMT1, Knezevich S.. ETV6 (ETS variant gene 6 (TEL oncogene)). DNMT3B and HDAC1 (Swiss-Prot). The NoRC Atlas Genet Cytogenet Oncol Haematol. June 2005 . URL: (nucleolar remodeling complex) comprises BAZ2A and http://AtlasGeneticsOncology.org/Genes/ETV6ID38.html SMARCA5. A mechanism for silencing active Panagopoulos I, Strombeck B, Isaksson M, Heldrup J, ribosomal RNA (rRNA) genes is the recruitment by Olofsson T, Johansson B.. Fusion of ETV6 with an intronic TTF1 (transcription termination factor-1) of NoRC to sequence of the BAZ2A gene in a paediatric pre-B acute the promoter of rRNAs in the nucleolus. PARP1, lymphoblastic leukaemia with a cryptic chromosome 12 rearrangement. Br J Haematol. 2006 May;133(3):270-5. component of the machinery that establishes and maintains silent rDNA chromatin during cell division, Manola KN, Georgakakos VN, Margaritis D, Stavropoulou C, binds to BAZ2A (Guetg et al., 2012). BAZ2A is up- Panos C, Kotsianidis I, Pantelias GE, Sambani C.. Disruption of the ETV6 gene as a consequence of a rare translocation regulated in patients with chronic lymphocytic (12;12)(p13;q13) in treatment-induced acute myeloid leukemia leukemia (Hanlon et al., 2009). after breast cancer. Cancer Genet Cytogenet. 2008 Jan 1;180(1):37-42. Result of the chromosomal Eguchi-Ishimae M, Eguchi M, Maki K, Porcher C, Shimizu R, Yamamoto M, Mitani K.. Leukemia-related transcription factor anomaly TEL/ETV6 expands erythroid precursors and stimulates hemoglobin synthesis. Cancer Sci. 2009 Apr;100(4):689-97. Hybrid gene doi: 10.1111/j.1349-7006.2009.01097.x. Epub 2009 Mar 11. Transcript Hanlon K, Rudin CE, Harries LW.. Investigating the targets of Transcript consisting of exons 1 and 2 of ETV6 and a MIR-15a and MIR-16-1 in patients with chronic lymphocytic leukemia (CLL). PLoS One. 2009 Sep 25;4(9):e7169. doi: sequence from intron 1 of BAZ2A. This transcript is 10.1371/journal.pone.0007169. not expected to produce any chimeric protein. Meester-Smoor MA, Janssen MJ, ter Haar WM, van Wely KH, Fusion protein Aarnoudse AJ, van Oord G, van Tilburg GB, Zwarthoff EC.. The ETS family member TEL binds to nuclear receptors RAR Description and RXR and represses gene activation. PLoS One. The transcript may encode a truncated form of ETV6, 2011;6(9):e23620. doi: 10.1371/journal.pone.0023620. Epub containing the first 54 amino acids (aa) of ETV6, 2011 Sep 16. followed by 16 aa from the 3' fusion sequence. Guetg C, Scheifele F, Rosenthal F, Hottiger MO, Santoro R.. Oncogenesis Inheritance of silent rDNA chromatin is mediated by PARP1 via The production of a truncated form of ETV6 is noncoding RNA. Mol Cell. 2012 Mar 30;45(6):790-800. doi: 10.1016/j.molcel.2012.01.024. Epub 2012 Mar 8. reminiscent of ETV6 fusions with MDS2, FCHO2, PER1, and STL, according to Panagopoulos et al., This article should be referenced as such: 2006. BAZ2A may also be deregulated. Huret JL. t(12;12)(p13;q13) ETV6/BAZ2A. Atlas Genet Cytogenet Oncol Haematol. 2013; 17(9):640-641. Atlas Genet Cytogenet Oncol Haematol. 2013; 17(9) 641 .
Recommended publications
  • Supplementary Table 1: Adhesion Genes Data Set

    Supplementary Table 1: Adhesion Genes Data Set

    Supplementary Table 1: Adhesion genes data set PROBE Entrez Gene ID Celera Gene ID Gene_Symbol Gene_Name 160832 1 hCG201364.3 A1BG alpha-1-B glycoprotein 223658 1 hCG201364.3 A1BG alpha-1-B glycoprotein 212988 102 hCG40040.3 ADAM10 ADAM metallopeptidase domain 10 133411 4185 hCG28232.2 ADAM11 ADAM metallopeptidase domain 11 110695 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 195222 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 165344 8751 hCG20021.3 ADAM15 ADAM metallopeptidase domain 15 (metargidin) 189065 6868 null ADAM17 ADAM metallopeptidase domain 17 (tumor necrosis factor, alpha, converting enzyme) 108119 8728 hCG15398.4 ADAM19 ADAM metallopeptidase domain 19 (meltrin beta) 117763 8748 hCG20675.3 ADAM20 ADAM metallopeptidase domain 20 126448 8747 hCG1785634.2 ADAM21 ADAM metallopeptidase domain 21 208981 8747 hCG1785634.2|hCG2042897 ADAM21 ADAM metallopeptidase domain 21 180903 53616 hCG17212.4 ADAM22 ADAM metallopeptidase domain 22 177272 8745 hCG1811623.1 ADAM23 ADAM metallopeptidase domain 23 102384 10863 hCG1818505.1 ADAM28 ADAM metallopeptidase domain 28 119968 11086 hCG1786734.2 ADAM29 ADAM metallopeptidase domain 29 205542 11085 hCG1997196.1 ADAM30 ADAM metallopeptidase domain 30 148417 80332 hCG39255.4 ADAM33 ADAM metallopeptidase domain 33 140492 8756 hCG1789002.2 ADAM7 ADAM metallopeptidase domain 7 122603 101 hCG1816947.1 ADAM8 ADAM metallopeptidase domain 8 183965 8754 hCG1996391 ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma) 129974 27299 hCG15447.3 ADAMDEC1 ADAM-like,
  • F-BAR Domain Only Protein 1 (FCHO1) Deficiency Is a Novel Cause of Combined Immune Deficiency in Human Subjects

    F-BAR Domain Only Protein 1 (FCHO1) Deficiency Is a Novel Cause of Combined Immune Deficiency in Human Subjects

    Letter to the Editor F-BAR domain only protein 1 (FCHO1) P5 was homozygous for the c.2711G>A mutation, which was deficiency is a novel cause of com- predicted to disrupt the intron 2 donor splice site and the correct bined immune deficiency in human FCHO1 amino acid sequence after Trp9 (Fig 1, B). No samples subjects were available to test the consequences of this mutation at the cDNA level. We performed quantitative PCR analysis of FCHO1 and To the Editor: FCHO2 expression in control CD41 and CD81 T cells, CD191 Clathrin-mediated endocytosis (CME) is the major endocytic B cells, CD561 natural killer cells, fibroblasts, and the K562 pathway by which eukaryotic cells internalize cell-surface cargo erythroleukemic cell line and observed differential expression. proteins and extracellular molecules, thereby enabling a broad FCHO1 was predominantly expressed in lymphoid cells, whereas range of biological processes, including cell signaling, nutrient FCHO2 was more abundantly expressed in fibroblasts and and growth factor uptake, and cell fate and differentiation.1 K562 cells (see Fig E3 in this article’s Online Repository at F-BAR domain only proteins 1 and 2 (FCHO1/FCHO2) are www.jacionline.org). involved in the maturation of clathrin-coated pit formation.2 To clarify the mechanisms underlying the T-cell lymphopenia Through the N-terminal F-BAR domain, they bind to observed in the patients, we first analyzed T-cell activation and phosphatidylinositol 4,5-biphosphate on the inner side of the proliferation in PBMCs from healthy control subjects and P2, the cell membrane, inducing and stabilizing membrane curvature.3 only patient from whom pre-HSCT PBMCs were available.
  • Mouse Fcho2 Knockout Project (CRISPR/Cas9)

    Mouse Fcho2 Knockout Project (CRISPR/Cas9)

    https://www.alphaknockout.com Mouse Fcho2 Knockout Project (CRISPR/Cas9) Objective: To create a Fcho2 knockout Mouse model (C57BL/6J) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Fcho2 gene (NCBI Reference Sequence: NM_172591 ; Ensembl: ENSMUSG00000041685 ) is located on Mouse chromosome 13. 26 exons are identified, with the ATG start codon in exon 1 and the TGA stop codon in exon 26 (Transcript: ENSMUST00000040340). Exon 3~5 will be selected as target site. Cas9 and gRNA will be co-injected into fertilized eggs for KO Mouse production. The pups will be genotyped by PCR followed by sequencing analysis. Note: Exon 3 starts from about 5.19% of the coding region. Exon 3~5 covers 15.25% of the coding region. The size of effective KO region: ~7005 bp. Page 1 of 9 https://www.alphaknockout.com Overview of the Targeting Strategy Wildtype allele 5' gRNA region gRNA region 3' 1 3 4 5 26 Legends Exon of mouse Fcho2 Knockout region Page 2 of 9 https://www.alphaknockout.com Overview of the Dot Plot (up) Window size: 15 bp Forward Reverse Complement Sequence 12 Note: The 2000 bp section upstream of Exon 3 is aligned with itself to determine if there are tandem repeats. No significant tandem repeat is found in the dot plot matrix. So this region is suitable for PCR screening or sequencing analysis. Overview of the Dot Plot (down) Window size: 15 bp Forward Reverse Complement Sequence 12 Note: The 2000 bp section downstream of Exon 5 is aligned with itself to determine if there are tandem repeats.
  • Integrating Protein Copy Numbers with Interaction Networks to Quantify Stoichiometry in Mammalian Endocytosis

    Integrating Protein Copy Numbers with Interaction Networks to Quantify Stoichiometry in Mammalian Endocytosis

    bioRxiv preprint doi: https://doi.org/10.1101/2020.10.29.361196; this version posted October 29, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. Integrating protein copy numbers with interaction networks to quantify stoichiometry in mammalian endocytosis Daisy Duan1, Meretta Hanson1, David O. Holland2, Margaret E Johnson1* 1TC Jenkins Department of Biophysics, Johns Hopkins University, 3400 N Charles St, Baltimore, MD 21218. 2NIH, Bethesda, MD, 20892. *Corresponding Author: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/2020.10.29.361196; this version posted October 29, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. Abstract Proteins that drive processes like clathrin-mediated endocytosis (CME) are expressed at various copy numbers within a cell, from hundreds (e.g. auxilin) to millions (e.g. clathrin). Between cell types with identical genomes, copy numbers further vary significantly both in absolute and relative abundance. These variations contain essential information about each protein’s function, but how significant are these variations and how can they be quantified to infer useful functional behavior? Here, we address this by quantifying the stoichiometry of proteins involved in the CME network. We find robust trends across three cell types in proteins that are sub- vs super-stoichiometric in terms of protein function, network topology (e.g.
  • Engineered Type 1 Regulatory T Cells Designed for Clinical Use Kill Primary

    Engineered Type 1 Regulatory T Cells Designed for Clinical Use Kill Primary

    ARTICLE Acute Myeloid Leukemia Engineered type 1 regulatory T cells designed Ferrata Storti Foundation for clinical use kill primary pediatric acute myeloid leukemia cells Brandon Cieniewicz,1* Molly Javier Uyeda,1,2* Ping (Pauline) Chen,1 Ece Canan Sayitoglu,1 Jeffrey Mao-Hwa Liu,1 Grazia Andolfi,3 Katharine Greenthal,1 Alice Bertaina,1,4 Silvia Gregori,3 Rosa Bacchetta,1,4 Norman James Lacayo,1 Alma-Martina Cepika1,4# and Maria Grazia Roncarolo1,2,4# Haematologica 2021 Volume 106(10):2588-2597 1Department of Pediatrics, Division of Stem Cell Transplantation and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, USA; 2Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, USA; 3San Raffaele Telethon Institute for Gene Therapy, Milan, Italy and 4Center for Definitive and Curative Medicine, Stanford School of Medicine, Stanford, CA, USA *BC and MJU contributed equally as co-first authors #AMC and MGR contributed equally as co-senior authors ABSTRACT ype 1 regulatory (Tr1) T cells induced by enforced expression of interleukin-10 (LV-10) are being developed as a novel treatment for Tchemotherapy-resistant myeloid leukemias. In vivo, LV-10 cells do not cause graft-versus-host disease while mediating graft-versus-leukemia effect against adult acute myeloid leukemia (AML). Since pediatric AML (pAML) and adult AML are different on a genetic and epigenetic level, we investigate herein whether LV-10 cells also efficiently kill pAML cells. We show that the majority of primary pAML are killed by LV-10 cells, with different levels of sensitivity to killing. Transcriptionally, pAML sensitive to LV-10 killing expressed a myeloid maturation signature.
  • Human Social Genomics in the Multi-Ethnic Study of Atherosclerosis

    Human Social Genomics in the Multi-Ethnic Study of Atherosclerosis

    Getting “Under the Skin”: Human Social Genomics in the Multi-Ethnic Study of Atherosclerosis by Kristen Monét Brown A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Epidemiological Science) in the University of Michigan 2017 Doctoral Committee: Professor Ana V. Diez-Roux, Co-Chair, Drexel University Professor Sharon R. Kardia, Co-Chair Professor Bhramar Mukherjee Assistant Professor Belinda Needham Assistant Professor Jennifer A. Smith © Kristen Monét Brown, 2017 [email protected] ORCID iD: 0000-0002-9955-0568 Dedication I dedicate this dissertation to my grandmother, Gertrude Delores Hampton. Nanny, no one wanted to see me become “Dr. Brown” more than you. I know that you are standing over the bannister of heaven smiling and beaming with pride. I love you more than my words could ever fully express. ii Acknowledgements First, I give honor to God, who is the head of my life. Truly, without Him, none of this would be possible. Countless times throughout this doctoral journey I have relied my favorite scripture, “And we know that all things work together for good, to them that love God, to them who are called according to His purpose (Romans 8:28).” Secondly, I acknowledge my parents, James and Marilyn Brown. From an early age, you two instilled in me the value of education and have been my biggest cheerleaders throughout my entire life. I thank you for your unconditional love, encouragement, sacrifices, and support. I would not be here today without you. I truly thank God that out of the all of the people in the world that He could have chosen to be my parents, that He chose the two of you.
  • Variability of Human Rdna

    Variability of Human Rdna

    cells Review Variability of Human rDNA Evgeny Smirnov *, Nikola Chmúrˇciaková , František Liška, Pavla Bažantová and Dušan Cmarko Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech Republic; [email protected] (N.C.); [email protected] (F.L.); [email protected] (P.B.); [email protected] (D.C.) * Correspondence: [email protected] Abstract: In human cells, ribosomal DNA (rDNA) is arranged in ten clusters of multiple tandem repeats. Each repeat is usually described as consisting of two parts: the 13 kb long ribosomal part, containing three genes coding for 18S, 5.8S and 28S RNAs of the ribosomal particles, and the 30 kb long intergenic spacer (IGS). However, this standard scheme is, amazingly, often altered as a result of the peculiar instability of the locus, so that the sequence of each repeat and the number of the repeats in each cluster are highly variable. In the present review, we discuss the causes and types of human rDNA instability, the methods of its detection, its distribution within the locus, the ways in which it is prevented or reversed, and its biological significance. The data of the literature suggest that the variability of the rDNA is not only a potential cause of pathology, but also an important, though still poorly understood, aspect of the normal cell physiology. Keywords: human rDNA; sequence variability; mutations; copy number 1. Introduction In human cells, ribosomal DNA (rDNA) is arranged in ten clusters of multiple tandem Citation: Smirnov, E.; repeats.
  • The Identification of Chromosomal Translocation, T(4;6)(Q22;Q15), in Prostate Cancer

    The Identification of Chromosomal Translocation, T(4;6)(Q22;Q15), in Prostate Cancer

    Prostate Cancer and Prostatic Diseases (2010) 13, 117–125 & 2010 Nature Publishing Group All rights reserved 1365-7852/10 www.nature.com/pcan ORIGINAL ARTICLE The identification of chromosomal translocation, t(4;6)(q22;q15), in prostate cancer L Shan1, L Ambroisine2, J Clark3,RJYa´n˜ez-Mun˜oz1, G Fisher2, SC Kudahetti1, J Yang1, S Kia1, X Mao1, A Fletcher3, P Flohr3, S Edwards3, G Attard3, J De-Bono3, BD Young1, CS Foster4, V Reuter5, H Moller6, TD Oliver1, DM Berney1, P Scardino7, J Cuzick2, CS Cooper3 and Y-J Lu1, on behalf of the Transatlantic Prostate Group 1Centre for Molecular Oncology and Imaging, Institute of Cancer, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK; 2Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK; 3Male Urological Cancer Research Centre, Institute of Cancer Research, Surrey, UK; 4Division of Cellular and Molecular Pathology, University of Liverpool, Liverpool, UK; 5Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 6King’s College London, Thames Cancer Registry, London, UK and 7Department of Urology, Memorial Sloan Kettering Cancer Center, New York, NY, USA Our previous work identified a chromosomal translocation t(4;6) in prostate cancer cell lines and primary tumors. Using probes located on 4q22 and 6q15, the breakpoints identified in LNCaP cells, we performed fluorescence in situ hybridization analysis to detect this translocation in a large series of clinical localized prostate cancer samples treated conservatively. We found that t(4;6)(q22;q15) occurred in 78 of 667 cases (11.7%).
  • Mutational Landscape and Interaction of SARS-Cov-2 with Host Cellular Components

    Mutational Landscape and Interaction of SARS-Cov-2 with Host Cellular Components

    microorganisms Review Mutational Landscape and Interaction of SARS-CoV-2 with Host Cellular Components Mansi Srivastava 1,†, Dwight Hall 1,†, Okiemute Beatrice Omoru 1, Hunter Mathias Gill 1, Sarah Smith 1 and Sarath Chandra Janga 1,2,3,* 1 Department of BioHealth Informatics, School of Informatics and Computing, Indiana University Purdue University Indianapolis, Informatics and Communications Technology Complex, 535 West Michigan Street, Indianapolis, IN 46202, USA; [email protected] (M.S.); [email protected] (D.H.); [email protected] (O.B.O.); [email protected] (H.M.G.); [email protected] (S.S.) 2 Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, 410 West 10th Street, Indianapolis, IN 46202, USA 3 Department of Medical and Molecular Genetics, Indiana University School of Medicine, Medical Research and Library Building, 975 West Walnut Street, Indianapolis, IN 46202, USA * Correspondence: [email protected]; Tel.: +1-317-278-4147; Fax: +1-317-278-9201 † Contributed equally. Abstract: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid evolution has led to a global health crisis. Increasing mutations across the SARS-CoV-2 genome have severely impacted the development of effective therapeutics and vaccines to combat the virus. However, the new SARS-CoV-2 variants and their evolutionary characteristics are not fully understood. Host cellular components such as the ACE2 receptor, RNA-binding proteins (RBPs), microRNAs, small nuclear RNA (snRNA), 18s rRNA, and the 7SL RNA component of the signal recognition particle (SRP) interact with various structural and non-structural proteins of the Citation: Srivastava, M.; Hall, D.; SARS-CoV-2.
  • Machine Learning-Based Identification and Cellular Validation of Tropomyosin 1 As a Genetic Inhibitor of Hematopoiesis

    Machine Learning-Based Identification and Cellular Validation of Tropomyosin 1 As a Genetic Inhibitor of Hematopoiesis

    bioRxiv preprint doi: https://doi.org/10.1101/631895; this version posted May 8, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Machine learning-based identification and cellular validation of Tropomyosin 1 as a genetic inhibitor of hematopoiesis. Thom CS1,2,3*, Jobaliya CD4,5, Lorenz K2,3, Maguire JA4,5, Gagne A4,5, Gadue P4,5, French DL4,5, Voight BF2,3,6* 1Division of Neonatology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA 2Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA 3Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA 4Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, PA, USA 5Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA 6Institute of Translational Medicine and Therapeutics, University of Pennsylvania, PA, USA *Corresponding authors: [email protected], [email protected] bioRxiv preprint doi: https://doi.org/10.1101/631895; this version posted May 8, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Introductory paragraph A better understanding of the genetic mechanisms regulating hematopoiesis are necessary, and could augment translational efforts to generate red blood cells (RBCs) and/or platelets in vitro.
  • Disruption of ETV6 in Intron 2 Results in Upregulatory and Insertional Events in Childhood Acute Lymphoblastic Leukaemia

    Disruption of ETV6 in Intron 2 Results in Upregulatory and Insertional Events in Childhood Acute Lymphoblastic Leukaemia

    Leukemia (2008) 22, 114–123 & 2008 Nature Publishing Group All rights reserved 0887-6924/08 $30.00 www.nature.com/leu ORIGINAL ARTICLE Disruption of ETV6 in intron 2 results in upregulatory and insertional events in childhood acute lymphoblastic leukaemia GR Jalali1,2,QAn1, ZJ Konn, H Worley, SL Wright, CJ Harrison, JC Strefford1 and M Martineau1 Leukaemia Research Cytogenetics Group, Cancer Sciences Division, University of Southampton, Southampton, UK We describe four cases of childhood B-cell progenitor acute more often involved when the 12p rearrangements are balanced lymphoblastic leukaemia (BCP-ALL) and one of T-cell (T-ALL) rather than unbalanced, the latter often being associated with a with unexpected numbers of interphase signals for ETV6 with complex karyotype.10,11 The inherent instability of the ETV6 an ETV6–RUNX1 fusion probe. Three fusion negative cases each had a telomeric part of 12p terminating within intron 2 of gene has been demonstrated in several different studies by the ETV6, attached to sequences from 5q, 7p and 7q, respectively. use of cosmid probes to its individual exons. However, the series Two fusion positive cases, with partial insertions of ETV6 into of probes used have not always covered the complete gene, so chromosome 21, also had a breakpoint in intron 2. Fluores- the significance of some findings is unclear.3,6–8 Although ETV6 cence in situ hybridisation (FISH), array comparative genomic is an attractive candidate for the main target of the deletions and hybridization (aCGH) and Molecular Copy-Number Counting translocations associated with 12p, its central role remains (MCC) results were concordant for the T-cell case.
  • Gene Section Review

    Gene Section Review

    Atlas of Genetics and Cytogenetics in Oncology and Haematology INIST -CNRS OPEN ACCESS JOURNAL Gene Section Review ETV6 (ets variant 6) Etienne De Braekeleer, Nathalie Douet-Guilbert, Marc De Braekeleer Cytogenetics Laboratory, Faculty of Medicine, University of Brest, France (EDB, NDG, MDB) Published in Atlas Database: March 2014 Online updated version : http://AtlasGeneticsOncology.org/Genes/ETV6ID38.html DOI: 10.4267/2042/54367 This article is an update of : Knezevich S. ETV6 (ETS variant gene 6 (TEL oncogene)). Atlas Genet Cytogenet Oncol Haematol 2005;9(4):272-275. Romana SP. ETV6 (ETS variant gene 6 (TEL oncogene)). Atlas Genet Cytogenet Oncol Haematol 1999;3(4):181-182. This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2014 Atlas of Genetics and Cytogenetics in Oncology and Haematology Abstract The ETV6 gene located at band 12p13 encodes a protein containing two major domains, the HLH (helix-loop-helix) domain, encoded by exons 3 and 4, and the ETS domain, encoded by exons 6 through 8, with in between the internal domain encoded by exon 5. ETV6 is a strong transcriptional ETV6 (12p13.2) in normal cells: clone dJ852F10 - repressor, acting through its HLH and internal Courtesy Mariano Rocchi, Resources for Molecular domains. Five potential mechanisms of ETV6- Cytogenetics. mediated carcinogenesis have been identified: constitutive activation of the kinase activity of the DNA/RNA partner protein, modification of the original functions of a transcription factor, loss of function Description of the fusion gene, affecting ETV6 and the partner A member of the ets (E-26 transforming specific) gene, activation of a proto-oncogene in the vicinity family of transcription factors; the gene spans a of a chromosomal translocation and dominant region of 240 kb and consists of 8 exons.