Abstract
The t(7;11)(p15;p15) translocation is a recurrent chromosomal abnormality associated primarily with acute myeloid leukaemia (FAB M2 and M4). We present here the molecular definition of this translocation. On chromosome 7 positional cloning revealed the consistent rearrangement of the HOXA9 gene, which encodes a class I homeodomain protein potentially involved in myeloid differentiation. On chromosome 11 the translocation targets the human homologue of NUP98, a member of the GLFG nucleoporin family. Chimaeric messages spliced over the breakpoint fuse the GLFG repeat domains of NUP98 in-frame to the HOXA9 homeobox. The predicted NUP98-HOXA9 fusion protein may promote leukaemogenesis through inhibition of HOXA9-mediated terminal differentiation and/or aberrant nucleocytoplasmic transport.
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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Amino Acid Sequence
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Base Sequence
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Chromosome Mapping
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Chromosomes, Human, Pair 11*
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Chromosomes, Human, Pair 7*
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Cloning, Molecular
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Homeodomain Proteins / genetics*
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Homeodomain Proteins / physiology
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Humans
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Leukemia, Myelomonocytic, Acute / genetics*
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Membrane Proteins / genetics*
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Molecular Sequence Data
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Nuclear Pore Complex Proteins*
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Nuclear Proteins / genetics*
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RNA, Messenger / genetics
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RNA, Neoplasm / genetics
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Repetitive Sequences, Nucleic Acid / genetics
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Sequence Analysis, DNA
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Translocation, Genetic*
Substances
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Homeodomain Proteins
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Membrane Proteins
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Nuclear Pore Complex Proteins
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Nuclear Proteins
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RNA, Messenger
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RNA, Neoplasm
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homeobox protein HOXA9
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nuclear pore complex protein 98
Associated data
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GENBANK/U41813
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GENBANK/U41814
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GENBANK/U41815