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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 |
2003-10-10
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pubmed:abstractText |
Loss-of-function alterations of INK4A are commonly observed in lymphoid malignancies, but are consistently absent in pre-B cell leukemias induced by the chimeric oncoprotein E2a-Pbx1 created by t(1;19) chromosomal translocations. We report here that experimental induction of E2a-Pbx1 enhances expression of BMI-1, a lymphoid oncogene whose product functions as a transcriptional repressor of the INK4A-ARF tumor suppressor locus. Bmi-1-deficient hematopoietic progenitors are resistant to transformation by E2a-Pbx1; however, the requirement for Bmi-1 is alleviated in cells deficient for both Bmi-1 and INK4A-ARF. Furthermore, the adverse effects of E2a-Pbx1 on pre-B cell survival and differentiation are partially bypassed by forced expression of p16(Ink4a). These results link E2a-Pbx1 with Bmi-1 on an oncogenic pathway that is likely to play a role in the pathogenesis of human lymphoid leukemias through downregulation of the INK4A-ARF gene.
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pubmed:grant |
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1097-2765
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
393-400
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:14536079-Apoptosis,
pubmed-meshheading:14536079-Blotting, Western,
pubmed-meshheading:14536079-Cell Aging,
pubmed-meshheading:14536079-Cell Line,
pubmed-meshheading:14536079-Cell Transformation, Neoplastic,
pubmed-meshheading:14536079-Cyclin-Dependent Kinase Inhibitor p16,
pubmed-meshheading:14536079-Diploidy,
pubmed-meshheading:14536079-Down-Regulation,
pubmed-meshheading:14536079-Fibroblasts,
pubmed-meshheading:14536079-Flow Cytometry,
pubmed-meshheading:14536079-Gene Expression Regulation,
pubmed-meshheading:14536079-Genotype,
pubmed-meshheading:14536079-Hematopoietic Stem Cells,
pubmed-meshheading:14536079-Homeodomain Proteins,
pubmed-meshheading:14536079-Humans,
pubmed-meshheading:14536079-Nuclear Proteins,
pubmed-meshheading:14536079-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:14536079-Oncogene Proteins, Fusion,
pubmed-meshheading:14536079-Proto-Oncogene Proteins,
pubmed-meshheading:14536079-Repressor Proteins,
pubmed-meshheading:14536079-Retroviridae,
pubmed-meshheading:14536079-Time Factors,
pubmed-meshheading:14536079-Transfection
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pubmed:year |
2003
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pubmed:articleTitle |
Bmi-1 regulation of INK4A-ARF is a downstream requirement for transformation of hematopoietic progenitors by E2a-Pbx1.
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pubmed:affiliation |
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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