Abstract
A partial nontandem duplication (PNTD) of mixed lineage leukemia (MLL) gene is described in B-cell acute lymphoid leukemia without structural cytogenetic abnormalities at 11q23 and 9p22. A duplicated portion of MLL is interrupted by the insertion of a region of 9p22 that includes the 3'-end of the AF9 gene. The PNTD encodes: (a) a PNTD transcript; (b) a partial tandem duplication of MLL; and (c) a chimeric transcript fusing MLL to the 3'-end of AF9, mimicking the t(9;11)(p22;q23) and expressed 1024-fold higher than the other two. The MLL PNTD, therefore, contributes toward leukemogenesis through simultaneous production of fusion transcripts that are otherwise encoded by three distinct genetic defects.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alternative Splicing / genetics
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Blotting, Southern
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Burkitt Lymphoma / genetics*
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Chromosome Breakage
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Chromosomes, Human, Pair 11 / genetics
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Chromosomes, Human, Pair 9 / genetics
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DNA-Binding Proteins / genetics*
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Exons
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Gene Rearrangement*
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Histone-Lysine N-Methyltransferase
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Humans
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Myeloid-Lymphoid Leukemia Protein
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Nuclear Proteins / genetics
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Proto-Oncogenes*
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RNA, Messenger / genetics*
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Recombinant Fusion Proteins / genetics
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Repetitive Sequences, Nucleic Acid
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Reverse Transcriptase Polymerase Chain Reaction
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Transcription Factors*
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Translocation, Genetic
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Tumor Cells, Cultured
Substances
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DNA-Binding Proteins
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KMT2A protein, human
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MLLT3 protein, human
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Nuclear Proteins
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RNA, Messenger
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Recombinant Fusion Proteins
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Transcription Factors
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Myeloid-Lymphoid Leukemia Protein
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Histone-Lysine N-Methyltransferase