| Common chromatin structures at breakpoint cluster regions may lead to chromosomal translocations found in chronic and acute leukemias. | |
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MedLine Citation:
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PMID: 16572268 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The t(9;22) BCR/ABL fusion is associated with over 90% of chronic myelogenous and 25% of acute lymphocytic leukemia. Chromosome 11q23 translocations in acute myeloid and lymphoid leukemia cells demonstrate myeloid lymphoid leukemia (MLL) fusions with over 40 gene partners, like AF9 and AF4 on chromosomes 9 and 4, respectively. Therapy-related leukemia is associated with the above gene rearrangements following the treatment with topoisomerase II (topo II) inhibitors. BCR, ABL, MLL, AF9 and AF4 have defined patient breakpoint cluster regions. Chromatin structural elements including topo II and DNase I cleavage sites and scaffold attachment sites have previously been shown to closely associate with the MLL and AF9 breakpoint cluster regions, implicating these elements in non-homologous recombination (NHR). In this report, using cell lines and primary cells, chromatin structural elements were analyzed in BCR, ABL and AF4 and, for comparison, in MLL2, which is a homolog to MLL, but not associated with chromosome translocations. Topo II and DNase I cleavage sites associated with all breakpoint cluster regions, whereas SARs associated with ABL and AF4, but not with BCR. No close breakpoint clustering with the topo II/DNase I sites were observed; however, a statistically significant 5' or 3' distribution of patient breakpoints to the topo II DNase I sites was found, implicating DNA repair and exonucleases. Although MLL2 was expressed in all cell lines tested, except for the presence of one DNAse I site in the promoter, no other structural elements were found in MLL2. A NHR model presented demonstrates the importance of chromatin structure in chromosome translocations involved with leukemia. |
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Authors:
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Reiner Strick; Yanming Zhang; Neelmini Emmanuel; Pamela L Strissel |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Validation Studies Date: 2006-03-30 |
Journal Detail:
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Title: Human genetics Volume: 119 ISSN: 0340-6717 ISO Abbreviation: Hum. Genet. Publication Date: 2006 Jun |
Date Detail:
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Created Date: 2006-05-03 Completed Date: 2006-12-01 Revised Date: 2012-06-25 |
Medline Journal Info:
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Nlm Unique ID: 7613873 Medline TA: Hum Genet Country: Germany |
Other Details:
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Languages: eng Pagination: 479-95 Citation Subset: IM |
Affiliation:
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Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA. reiner.strick@gyn.imed.uni-erlangen.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acute Disease Cell Line, Tumor Cells, Cultured Chromatin / chemistry*, enzymology, genetics Chromosome Breakage* Chromosomes, Human / genetics* Chronic Disease Humans K562 Cells Leukemia / enzymology, genetics*, metabolism* Proto-Oncogene Proteins c-bcr / chemistry, genetics Recombination, Genetic Translocation, Genetic* |
| Chemical | |
Reg. No./Substance:
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0/Chromatin; EC 2.7.11.1/BCR protein, human; EC 2.7.11.1/Proto-Oncogene Proteins c-bcr |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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