Publikation:

LMO2 activation by deacetylation is indispensable for hematopoiesis and T-ALL leukemogenesis

Vorschaubild

Dateien

Morishima_2-11vfm9s57gddu5.pdf
Morishima_2-11vfm9s57gddu5.pdfGröße: 1.11 MBDownloads: 41

Datum

2019

Autor:innen

Morishima, Tatsuya
Krahl, Ann-Christin
Nasri, Masoud
Xu, Yun
Aghaallaei, Narges
Findik, Betül
Klimiankou, Maksim
Ritter, Malte
Skokowa, Julia
et al.

Herausgeber:innen

Kontakt

ISSN der Zeitschrift

Electronic ISSN

ISBN

Bibliografische Daten

Verlag

Schriftenreihe

Auflagebezeichnung

URI (zitierfähiger Link)
http://nbn-resolving.de/urn:nbn:de:bsz:352-2-11vfm9s57gddu5
DOI (zitierfähiger Link)
https://doi.org/10.1182/blood.2019000095
ArXiv-ID

Internationale Patentnummer

Link zur Lizenz
Urheberrechtlich geschützt

Angaben zur Forschungsförderung

Projekt

Open Access-Veröffentlichung
Open Access Green

Sammlungen

Biologie: Publikationen
Core Facility der Universität Konstanz

Gesperrt bis

Titel in einer weiteren Sprache

Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published

Erschienen in

Blood. American Society of Hematology. 2019, 134(14), pp. 1159-1175. ISSN 0006-4971. eISSN 1528-0020. Available under: doi: 10.1182/blood.2019000095

Zusammenfassung

Hematopoietic transcription factor LIM domain only 2 (LMO2), a member of the TAL1 transcriptional complex, plays an essential role during early hematopoiesis and is frequently activated in T-cell acute lymphoblastic leukemia (T-ALL) patients. Here, we demonstrate that LMO2 is activated by deacetylation on lysine 74 and 78 via the nicotinamide phosphoribosyltransferase (NAMPT)/sirtuin 2 (SIRT2) pathway. LMO2 deacetylation enables LMO2 to interact with LIM domain binding 1 and activate the TAL1 complex. NAMPT/SIRT2-mediated activation of LMO2 by deacetylation appears to be important for hematopoietic differentiation of induced pluripotent stem cells and blood formation in zebrafish embryos. In T-ALL, deacetylated LMO2 induces expression of TAL1 complex target genes HHEX and NKX3.1 as well as LMO2 autoregulation. Consistent with this, inhibition of NAMPT or SIRT2 suppressed the in vitro growth and in vivo engraftment of T-ALL cells via diminished LMO2 deacetylation. This new molecular mechanism may provide new therapeutic possibilities in T-ALL and may contribute to the development of new methods for in vitro generation of blood cells.

Zusammenfassung in einer weiteren Sprache

Fachgebiet (DDC)
570 Biowissenschaften, Biologie

Schlagwörter

adult t-cell lymphoma/leukemia, hematopoiesis, t-cell leukemia, acute, leukemogenesis, zebrafish, lysine, idiopathic pneumonia syndrome, embryo

Konferenz

Rezension
undefined / . - undefined, undefined

Forschungsvorhaben

Organisationseinheiten

Zeitschriftenheft

Zugehörige Datensätze in KOPS

Zitieren

ISO 690MORISHIMA, Tatsuya, Ann-Christin KRAHL, Masoud NASRI, Yun XU, Narges AGHAALLAEI, Betül FINDIK, Maksim KLIMIANKOU, Malte RITTER, Patrick MÜLLER, Julia SKOKOWA, 2019. LMO2 activation by deacetylation is indispensable for hematopoiesis and T-ALL leukemogenesis. In: Blood. American Society of Hematology. 2019, 134(14), pp. 1159-1175. ISSN 0006-4971. eISSN 1528-0020. Available under: doi: 10.1182/blood.2019000095
BibTex
@article{Morishima2019activ-56290,
  year={2019},
  doi={10.1182/blood.2019000095},
  title={LMO2 activation by deacetylation is indispensable for hematopoiesis and T-ALL leukemogenesis},
  number={14},
  volume={134},
  issn={0006-4971},
  journal={Blood},
  pages={1159--1175},
  author={Morishima, Tatsuya and Krahl, Ann-Christin and Nasri, Masoud and Xu, Yun and Aghaallaei, Narges and Findik, Betül and Klimiankou, Maksim and Ritter, Malte and Müller, Patrick and Skokowa, Julia}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/56290">
    <dc:contributor>Morishima, Tatsuya</dc:contributor>
    <dc:creator>Klimiankou, Maksim</dc:creator>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/56290/1/Morishima_2-11vfm9s57gddu5.pdf"/>
    <dc:contributor>Müller, Patrick</dc:contributor>
    <dcterms:issued>2019</dcterms:issued>
    <dc:contributor>Xu, Yun</dc:contributor>
    <dc:creator>Krahl, Ann-Christin</dc:creator>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-01-21T12:03:40Z</dc:date>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/56290"/>
    <dc:creator>Aghaallaei, Narges</dc:creator>
    <dc:contributor>Findik, Betül</dc:contributor>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-01-21T12:03:40Z</dcterms:available>
    <dc:rights>terms-of-use</dc:rights>
    <dc:creator>Findik, Betül</dc:creator>
    <dc:contributor>Skokowa, Julia</dc:contributor>
    <dcterms:abstract xml:lang="eng">Hematopoietic transcription factor LIM domain only 2 (LMO2), a member of the TAL1 transcriptional complex, plays an essential role during early hematopoiesis and is frequently activated in T-cell acute lymphoblastic leukemia (T-ALL) patients. Here, we demonstrate that LMO2 is activated by deacetylation on lysine 74 and 78 via the nicotinamide phosphoribosyltransferase (NAMPT)/sirtuin 2 (SIRT2) pathway. LMO2 deacetylation enables LMO2 to interact with LIM domain binding 1 and activate the TAL1 complex. NAMPT/SIRT2-mediated activation of LMO2 by deacetylation appears to be important for hematopoietic differentiation of induced pluripotent stem cells and blood formation in zebrafish embryos. In T-ALL, deacetylated LMO2 induces expression of TAL1 complex target genes HHEX and NKX3.1 as well as LMO2 autoregulation. Consistent with this, inhibition of NAMPT or SIRT2 suppressed the in vitro growth and in vivo engraftment of T-ALL cells via diminished LMO2 deacetylation. This new molecular mechanism may provide new therapeutic possibilities in T-ALL and may contribute to the development of new methods for in vitro generation of blood cells.</dcterms:abstract>
    <dc:creator>Morishima, Tatsuya</dc:creator>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:contributor>Nasri, Masoud</dc:contributor>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/56290/1/Morishima_2-11vfm9s57gddu5.pdf"/>
    <dc:contributor>Aghaallaei, Narges</dc:contributor>
    <dc:contributor>Klimiankou, Maksim</dc:contributor>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dcterms:title>LMO2 activation by deacetylation is indispensable for hematopoiesis and T-ALL leukemogenesis</dcterms:title>
    <dc:creator>Xu, Yun</dc:creator>
    <dc:contributor>Krahl, Ann-Christin</dc:contributor>
    <dc:creator>Skokowa, Julia</dc:creator>
    <dc:creator>Ritter, Malte</dc:creator>
    <dc:contributor>Ritter, Malte</dc:contributor>
    <dc:creator>Nasri, Masoud</dc:creator>
    <dc:language>eng</dc:language>
    <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/>
    <dc:creator>Müller, Patrick</dc:creator>
  </rdf:Description>
</rdf:RDF>

Interner Vermerk

xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter

Kontakt
URL der Originalveröffentl.

Prüfdatum der URL

Prüfungsdatum der Dissertation

Finanzierungsart

Kommentar zur Publikation

Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Nein
Begutachtet
Ja
Diese Publikation teilen