Kuwada N, Kimura F, Matsumura T, Yamashita T, Nakamura Y, Wakimoto N, Ikeda T, Sato K, Motoyoshi K
Third Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Cancer Res. 2001 Mar 15;61(6):2665-9.
More than 20 different partner genes with MLL have been cloned from leukemia cells with translocations involving chromosome 11 band q23 (11q23). All reported partner genes fused in-frame to MLL and the fusion cDNA encode chimeric MLL proteins with a significant portion derived from the partner genes. We analyzed one patient with de novo acute monoblastic leukemia with t(11;14)(q23;q24) and identified that a human homologue of gephyrin (human gephyrin) fused with MLL. Gephyrin is a rat glycine receptor-associated protein, which forms submembranous complexes and anchor glycine or gamma-aminobutyric acidA receptors to microtubules. Alternative splicing of human gephyrin gene created two different forms of fusion cDNA. In one form, human gephyrin gene fused in-frame to MLL exon 9, and the chimeric product had COOH terminus of human gephyrin protein, including the tubulin binding site. In the other, the reading frame terminated shortly after the fusion point. As a result, only seven amino acids with no known function were attached to the NH2 terminus of MLL protein. The functional significance of this de facto truncated MLL gene product is not clear.
超过20种与MLL相关的不同伙伴基因已从涉及11号染色体q23带（11q23）易位的白血病细胞中克隆出来。所有报道的伙伴基因均与MLL框内融合，且融合cDNA编码嵌合MLL蛋白，其中很大一部分来源于伙伴基因。我们分析了1例患有t(11;14)(q23;q24)的初发急性单核细胞白血病患者，发现一种人桥连蛋白（人桥连蛋白）的同源物与MLL融合。桥连蛋白是一种大鼠甘氨酸受体相关蛋白，可形成膜下复合物并将甘氨酸或γ-氨基丁酸A受体锚定到微管上。人桥连蛋白基因的可变剪接产生了两种不同形式的融合cDNA。在一种形式中，人桥连蛋白基因与MLL外显子9框内融合，嵌合产物具有人桥连蛋白的COOH末端，包括微管蛋白结合位点。在另一种形式中，阅读框在融合点后不久终止。结果，只有7个无已知功能的氨基酸连接到MLL蛋白的NH2末端。这种实际上截短的MLL基因产物的功能意义尚不清楚。
