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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2011-2-9
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pubmed:abstractText |
The oncogenic fusion protein E2A-HLF is a chimeric transcription factor that arises from the t(17;19) translocation in childhood B-cell acute lymphoblastic leukemias (B-precursor ALL) and is associated with very poor outcome. We show that retroviral-mediated expression of E2A-HLF alone is sufficient to immortalize primary lymphoid progenitors. We identify Lmo2 and Bcl-2 as direct target genes downstream of E2A-HLF. We use real-time PCR analysis to show that LMO2 and BCL-2 expression is preferentially upregulated both in biopsy material from t(17;19) B-precursor ALL patients and lymphoid cell lines derived from t(17;19) leukemias. Co-expression of Lmo2 and Bcl-2 was sufficient to immortalize lymphoid progenitor cells resulting in a similar phenotype to that induced by E2A-HLF alone. Both shRNA-mediated knockdown of Lmo2 expression and pharmacological inhibition of BCL-2 function in E2A-HLF immortalized cells severely compromised their viability. These data suggest that both Lmo2 and Bcl-2 are required for the action of E2A-HLF in leukemogenesis.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/E2a-Hlf fusion protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/LIM Domain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/LMO2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins, Fusion,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1476-5551
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
321-30
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:21072044-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:21072044-Animals,
pubmed-meshheading:21072044-Cell Survival,
pubmed-meshheading:21072044-Cell Transformation, Neoplastic,
pubmed-meshheading:21072044-DNA-Binding Proteins,
pubmed-meshheading:21072044-Hematopoietic Stem Cells,
pubmed-meshheading:21072044-Humans,
pubmed-meshheading:21072044-LIM Domain Proteins,
pubmed-meshheading:21072044-Leukemia,
pubmed-meshheading:21072044-Metalloproteins,
pubmed-meshheading:21072044-Mice,
pubmed-meshheading:21072044-Oncogene Proteins, Fusion,
pubmed-meshheading:21072044-Proto-Oncogene Proteins,
pubmed-meshheading:21072044-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:21072044-Retroviridae,
pubmed-meshheading:21072044-Transcription Factors,
pubmed-meshheading:21072044-Transfection,
pubmed-meshheading:21072044-Up-Regulation
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pubmed:year |
2011
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pubmed:articleTitle |
The E2A-HLF oncogenic fusion protein acts through Lmo2 and Bcl-2 to immortalize hematopoietic progenitors.
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pubmed:affiliation |
Molecular Haematology and Cancer Biology Unit, Institute of Child Health, University College London, London, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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