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- W2117002977 endingPage "1679" @default.
- W2117002977 startingPage "1671" @default.
- W2117002977 abstract "The human AF9 gene at 9p22 is one of the most common fusion partner genes with the MLL gene at 11q23, resulting in the t(9;11)(p22;q23). The MLL-AF9 fusion gene is associated with de novo acute myelo-genous leukemia (AML), rarely with acute lymphocytic leukemia (ALL) and with therapy related leukemia (t-AML). The AF9 gene is >100 kb and two patient breakpoint cluster regions (BCRs) have been identified; BCR1 is within intron 4, previously called site A, whereas BCR2 or site B spans introns 7 and 8. Patient breakpoint locations were determined previously by RT-PCR and by genomic DNA cloning. In this study, we defined the exon-intron boundaries and identified several different structural elements in AF9 including a co-localizing in vivo DNA topo II cleavage site and an in vitro DNase I hypersensitive (DNase 1 HS) site in intron 7 in BCR2. Reversibility experiments demonstrated a religation of the topo II cleavage sites. The location of the in vivo topo II cleavage site was confirmed in vitro using a topo II cleavage assay. In addition, two scaffold associated regions (SARs) are located centromeric to the topo II and DNase I HS cleavage sites and border both patient breakpoint regions: SAR1 is located in intron 4, whereas SAR2 encompasses parts of exons 5-7. This study demonstrates that the patient breakpoint regions of AF9 share the same structural elements as the MLL BCR. We describe a DNA breakage and repair model for non-homologous recombination between MLL and its partner genes, particularly AF9." @default.
- W2117002977 created "2016-06-24" @default.
- W2117002977 creator A5004347976 @default.
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- W2117002977 creator A5046425794 @default.
- W2117002977 creator A5053666722 @default.
- W2117002977 creator A5070734184 @default.
- W2117002977 date "2000-07-01" @default.
- W2117002977 modified "2023-09-26" @default.
- W2117002977 title "DNA structural properties of AF9 are similar to MLL and could act as recombination hot spots resulting in MLL/AF9 translocations and leukemogenesis" @default.
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- W2117002977 doi "https://doi.org/10.1093/hmg/9.11.1671" @default.
- W2117002977 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10861294" @default.
- W2117002977 hasPublicationYear "2000" @default.
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