title: Fusion of the MLL gene with two different genes, AF-6 and AF-5alpha, by a complex translocation involving chromosomes 5, 6, 8 and 11 in infant leukemia.
abstract: We analysed a complex translocation involving chromosomes 5, 6, 8 and 11 in a case of infant leukemia. Molecular analysis of the MLL gene revealed that MLL was fused with two different genes, AF-6 on chromosome 6q27 and AF-5alpha. AF-5alpha, the 11th partner gene fused with MLL, is a novel gene mapped to chromosome 5q12, which encodes a 31 kDa protein of 269 amino acids and contains a possible nuclear targeting sequence, a potential leucine zipper dimerization motif and an alpha-helical coiled-coil domain. In situ hybridization and molecular cloning analyses demonstrated that two different types of chromosomal recombination had occurred in the cells. One was a three-way translocation among chromosomes 6, 8 and 11, and the other was an insertion of a chromosome 5-derived segment into the breakpoint of chromosomes 8 and 11. Accordingly, the karyotype was defined as del(5)(q11.2q12), der(6)t(6;8) (q27;q11.2), der(8)(8pter-->8q11.2::5q11.2-->5q12::11q23-->++ +11qter), der(11)t(6;11) (q27;q23). Thus, the MLL gene created two different fusion mRNAs, since the chromosome 11 split into two different chromosomes 5 and 6. This is the first report demonstrating fusion of the MLL gene with two different genes by a complex translocation.
authors.affiliation: Biology Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Taki
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
authors.forename: M
authors.initials: M
authors.lastname: Taniwaki
authors.forename: M
authors.initials: M
authors.lastname: Seto
authors.forename: R
authors.initials: R
authors.lastname: Ueda
authors.forename: R
authors.initials: R
authors.lastname: Hanada
authors.forename: K
authors.initials: K
authors.lastname: Suzukawa
authors.forename: J
authors.initials: J
authors.lastname: Yokota
authors.forename: K
authors.initials: K
authors.lastname: Morishita
mesh_terms: D001483:Base Sequence; D015152:Blotting, Northern; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D016547:Kinesins / Q000235:genetics*; D007948:Leukemia, Monocytic, Acute / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D009218:Myosins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics* / Q000302:isolation & purification; D011519:Proto-Oncogenes; D014157:Transcription Factors; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: C095516:AFDN protein, human; C102640:CENPK protein, human; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D009218:Myosins; D016547:Kinesins