Taki T, Hayashi Y, Taniwaki M, Seto M, Ueda R, Hanada R, Suzukawa K, Yokota J, Morishita K
Biology Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Oncogene. 1996 Nov 21;13(10):2121-30.
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.
我们分析了一例婴儿白血病患者中涉及5号、6号、8号和11号染色体的复杂易位。对MLL基因的分子分析显示，MLL与两个不同的基因融合，即位于6q27的AF - 6和AF - 5α。AF - 5α是与MLL融合的第11个伙伴基因，是一个定位于5q12的新基因，它编码一个由269个氨基酸组成的31 kDa蛋白，包含一个可能的核靶向序列、一个潜在的亮氨酸拉链二聚化基序和一个α - 螺旋卷曲螺旋结构域。原位杂交和分子克隆分析表明，细胞中发生了两种不同类型的染色体重组。一种是6号、8号和11号染色体之间的三向易位，另一种是5号染色体衍生片段插入8号和11号染色体的断点处。因此，核型被定义为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)。因此，由于11号染色体分裂成两个不同的5号和6号染色体，MLL基因产生了两种不同的融合mRNA。这是首次报道通过复杂易位使MLL基因与两个不同基因融合。
