| Combined effects of the two reciprocal t(4;11) fusion proteins MLL.AF4 and AF4.MLL confer resistance to apoptosis, cell cycling capacity and growth transformation. | |
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MedLine Citation:
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PMID: 17130830 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The reciprocal chromosomal translocation t(4;11) is correlated with infant, childhood, adult and therapy-related high-risk acute leukemia. Here, we investigated the biological effects of MLL.AF4, AF4.MLL or the combination of both reciprocal fusion proteins in a conditional in vitro cell culture model system. Several parameters like cell growth, cell cycling capacity, apoptotic behavior and growth transformation were investigated under physiological and stress conditions. Co-transfected cells displayed the highest resistance against apoptotic triggers, cell cycling capacity and loss-of-contact inhibition. These analyses were complemented by gene expression profiling experiments and specific gene signatures were established for each of the three cell lines. Interestingly, co-transfected cells strongly upregulate the homeobox gene Nanog. In combination with Oct4, the Nanog homeoprotein is steering maintenance of pluripotency and self-renewal in embryonic stem cells. Transcription of Nanog and other stem cell factors, like Oct4 and Bmi1, was verified in biopsy material of t(4;11) patient cells which express both reciprocal t(4;11) fusion genes. In conclusion, the presence of both reciprocal MLL fusion proteins confers biological properties known from t(4;11) leukemia, suggesting that each of the two fusion proteins contribute specific properties and, in combination, also synergistic effects to the leukemic phenotype. |
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Authors:
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A Gaussmann; T Wenger; I Eberle; A Bursen; S Bracharz; I Herr; T Dingermann; R Marschalek |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-11-27 |
Journal Detail:
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Title: Oncogene Volume: 26 ISSN: 0950-9232 ISO Abbreviation: Oncogene Publication Date: 2007 May |
Date Detail:
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Created Date: 2007-05-17 Completed Date: 2007-06-18 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
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Languages: eng Pagination: 3352-63 Citation Subset: IM |
Affiliation:
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Institute of Pharmaceutical Biology/ZAFES, JWG-University Frankfurt, Biocenter, Frankfurt/Main, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis* Cell Cycle* Cells, Cultured Chromosomes, Human, Pair 4 / genetics* Cyclin-Dependent Kinase Inhibitor Proteins / genetics Gene Expression Profiling Humans Mice Mutation / genetics Myeloid-Lymphoid Leukemia Protein / genetics*, metabolism* Oncogene Proteins, Fusion / genetics*, metabolism* Polymerase Chain Reaction Transcription Factors / genetics |
| Chemical | |
Reg. No./Substance:
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0/Cyclin-Dependent Kinase Inhibitor Proteins; 0/MLL-AF4 fusion protein, human; 0/Oncogene Proteins, Fusion; 0/Transcription Factors; 149025-06-9/Myeloid-Lymphoid Leukemia Protein |
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