| Down-regulation of DLX3 expression in MLL-AF4 childhood lymphoblastic leukemias is mediated by promoter region hypermethylation. | |
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MedLine Citation:
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PMID: 17611665 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hypermethylation of CpG islands is the most well defined epigenetic change in neoplasia and plays an important role in the inactivation or silencing of cancer related genes. DLX genes (1-7), with large CpG islands in their 5' region, are implicated in a number of processes among which haematopoiesis. They are characterized by highly dynamic spatio-temporal expression and supposed to be involved in resistance to apoptosis of several tumor cell lines. In acute lymphoblastic leukemia (ALL) hypermethylation is a common phenomenon frequently associated with poor prognosis in specific genetic childhood leukemia subgroups. These data together with the presence of large CpG islands in the up-stream regions of the DLX genes make them attractive candidates for methylation regulated gene expression and leukemia related aberrancies. To validate the role of DLX genes in paediatric B-ALL cells, we studied two cell lines and two groups of patients with paediatric chromosomal rearrangements: MLL-AF4 and TEL-AML1, respectively. Analysis of methylation and gene expression patterns of DLX3 in 64 specimens of B-lineage ALL revealed that DLX3 presents aberrant methylation in paediatric B-ALL patients. In vitro experiments with 5-Aza-2'dC on leukemia cell lines, confirmed by Western blot analysis, indicated that the methylation of DLX3 CpG islands has a functional role and interferes with the DLX3 gene and DLX3 protein expression in B-ALL cells. Importantly, hypermethylation of DLX3 significantly reduces its expression in MLL-AF4 rearranged leukemias while methylation is almost absent in TEL-AML1 positive ALL specimens. These results show that differential DLX3 methylation could be a new epigenetic marker for genotypic B-cell leukemia subgroup with high-risk features. |
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Authors:
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Marta Campo Dell'Orto; Barbara Banelli; Emanuela Giarin; Benedetta Accordi; Luca Trentin; Massimo Romani; Geertruy te Kronnie; Giuseppe Basso |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Oncology reports Volume: 18 ISSN: 1021-335X ISO Abbreviation: Oncol. Rep. Publication Date: 2007 Aug |
Date Detail:
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Created Date: 2007-07-05 Completed Date: 2007-09-11 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 9422756 Medline TA: Oncol Rep Country: Greece |
Other Details:
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Languages: eng Pagination: 417-23 Citation Subset: IM |
Affiliation:
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Department of Paediatrics, University of Padova, I-35128 Padova, Italy. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Blotting, Western Burkitt Lymphoma / genetics, metabolism, pathology* Cell Line, Tumor Child DNA Methylation* Down-Regulation Gene Expression Regulation, Neoplastic HL-60 Cells Homeodomain Proteins / genetics*, metabolism Humans Myeloid-Lymphoid Leukemia Protein / genetics* Oncogene Proteins, Fusion / genetics* Promoter Regions, Genetic / genetics* Reverse Transcriptase Polymerase Chain Reaction / methods Transcription Factors / genetics*, metabolism U937 Cells |
| Chemical | |
Reg. No./Substance:
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0/Distal-less homeobox proteins; 0/Homeodomain Proteins; 0/MLL-AF4 fusion protein, human; 0/Oncogene Proteins, Fusion; 0/Transcription Factors; 149025-06-9/Myeloid-Lymphoid Leukemia Protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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