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Article: Distinct leukemia phenotypes in transgenic mice and different corepressor interactions generated by promyelocytic leukemia variant fusion genes PLZF-RARα and NPM-RARα

TitleDistinct leukemia phenotypes in transgenic mice and different corepressor interactions generated by promyelocytic leukemia variant fusion genes PLZF-RARα and NPM-RARα
Authors
Issue Date1999
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 1999, v. 96 n. 11, p. 6318-6323 How to Cite?
Abstract
Acute promyelocytic leukemia (APL) is characterized by a specific chromosome translocation involving RARα and one of four fusion partners: PML, PLZF, NPM, and NuMA genes. To study the leukemogenic potential of the fusion genes in vivo, we generated transgenic mice with PLZF-RARα and NPM- RARα. PLZF-RARα transgenic animals developed chronic myeloid leukemia-like phenotypes at an early stage of life (within 3 months in five of six mice), whereas three NPM-RARα transgenic mice showed a spectrum of phenotypes from typical APL to chronic myeloid leukemia relatively late in life (from 12 to 15 months). In contrast to bone marrow cells from PLZF-RARα transgenic mice, those from NPM-RARα transgenic mice could be induced to differentiate by all-trans-retinoic acid (ATRA). We also studied RARE binding properties and interactions between nuclear corepressor SMRT and various fusion proteins in response to ATRA. Dissociation of SMRT from different receptors was observed at ATRA concentrations of 0.01 μM, 0.1 μM, and 1.0 μM for RARα-RXRα, NPM-RARα, and PML-RARα, respectively, but not observed for PLZF-RARα even in the presence of 10 μM ATRA. We also determined the expression of the tissue factor gene in transgenic mice, which was detected only in bone marrow cells of mice expressing the fusion genes. These data clearly establish the leukemogenic role of PLZF-RARα and NPM-RARα and the importance of fusion receptor/corepressor interactions in the pathogenesis as well as in determining different clinical phenotypes of APL.
Persistent Identifierhttp://hdl.handle.net/10722/49415
ISSN
2013 Impact Factor: 9.809
PubMed Central ID
ISI Accession Number ID
References

 

Author Affiliations
  1. Shanghai Liver Disease Research Center
  2. Yangzhou University
  3. Institute of Cancer Research London
  4. The Mount Sinai Medical Center
  5. The University of Hong Kong
  6. Shanghai Second Medical University
  7. Ruijin Hospital
DC FieldValueLanguage
dc.contributor.authorCheng, GXen_HK
dc.contributor.authorZhu, XHen_HK
dc.contributor.authorMen, XQen_HK
dc.contributor.authorWang, Len_HK
dc.contributor.authorHuang, QHen_HK
dc.contributor.authorJin, XLen_HK
dc.contributor.authorXiong, SMen_HK
dc.contributor.authorZhu, Jen_HK
dc.contributor.authorGuo, WMen_HK
dc.contributor.authorChen, JQen_HK
dc.contributor.authorXu, SFen_HK
dc.contributor.authorSo, Een_HK
dc.contributor.authorChan, LCen_HK
dc.contributor.authorWaxman, Sen_HK
dc.contributor.authorZelent, Aen_HK
dc.contributor.authorChen, GQen_HK
dc.contributor.authorDong, Sen_HK
dc.contributor.authorLiu, JXen_HK
dc.contributor.authorChen, SJen_HK
dc.date.accessioned2008-06-12T06:42:00Z-
dc.date.available2008-06-12T06:42:00Z-
dc.date.issued1999en_HK
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 1999, v. 96 n. 11, p. 6318-6323en_HK
dc.identifier.issn0027-8424en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49415-
dc.description.abstractAcute promyelocytic leukemia (APL) is characterized by a specific chromosome translocation involving RARα and one of four fusion partners: PML, PLZF, NPM, and NuMA genes. To study the leukemogenic potential of the fusion genes in vivo, we generated transgenic mice with PLZF-RARα and NPM- RARα. PLZF-RARα transgenic animals developed chronic myeloid leukemia-like phenotypes at an early stage of life (within 3 months in five of six mice), whereas three NPM-RARα transgenic mice showed a spectrum of phenotypes from typical APL to chronic myeloid leukemia relatively late in life (from 12 to 15 months). In contrast to bone marrow cells from PLZF-RARα transgenic mice, those from NPM-RARα transgenic mice could be induced to differentiate by all-trans-retinoic acid (ATRA). We also studied RARE binding properties and interactions between nuclear corepressor SMRT and various fusion proteins in response to ATRA. Dissociation of SMRT from different receptors was observed at ATRA concentrations of 0.01 μM, 0.1 μM, and 1.0 μM for RARα-RXRα, NPM-RARα, and PML-RARα, respectively, but not observed for PLZF-RARα even in the presence of 10 μM ATRA. We also determined the expression of the tissue factor gene in transgenic mice, which was detected only in bone marrow cells of mice expressing the fusion genes. These data clearly establish the leukemogenic role of PLZF-RARα and NPM-RARα and the importance of fusion receptor/corepressor interactions in the pathogenesis as well as in determining different clinical phenotypes of APL.en_HK
dc.format.extent384 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_HK
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_HK
dc.rightsNational Academy of Sciences Proceedings. Copyright © National Academy of Sciences.en_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshDNA-Binding Proteins - geneticsen_HK
dc.subject.meshLeukemia, Promyelocytic, Acute - genetics - pathology - physiopathologyen_HK
dc.subject.meshOncogene Proteins, Fusion - geneticsen_HK
dc.subject.meshReceptors, Retinoic Acid - geneticsen_HK
dc.subject.meshTranscription Factors - geneticsen_HK
dc.titleDistinct leukemia phenotypes in transgenic mice and different corepressor interactions generated by promyelocytic leukemia variant fusion genes PLZF-RARα and NPM-RARαen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0027-8424&volume=96&issue=11&spage=6318&epage=6323&date=1999&atitle=Distinct+leukemia+phenotypes+in+transgenic+mice+and+different+corepressor+interactions+generated+by+promyelocytic+leukemia+variant+fusion+genes+PLZF-RARα+and+NPM-RARαen_HK
dc.identifier.emailChan, LC:chanlc@hkucc.hku.hken_HK
dc.identifier.authorityChan, LC=rp00373en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1073/pnas.96.11.6318en_HK
dc.identifier.pmid10339585en_HK
dc.identifier.pmcidPMC26879en_HK
dc.identifier.scopuseid_2-s2.0-13044268455en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-13044268455&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume96en_HK
dc.identifier.issue11en_HK
dc.identifier.spage6318en_HK
dc.identifier.epage6323en_HK
dc.identifier.isiWOS:000080527100074-
dc.publisher.placeUnited Statesen_HK

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