Gillert E, Leis T, Repp R, Reichel M, Hösch A, Breitenlohner I, Angermüller S, Borkhardt A, Harbott J, Lampert F, Griesinger F, Greil J, Fey G H, Marschalek R
Chair of Genetics, University of Erlangen-Nürnberg, Staudtstr. 5, D-91058 Erlangen, Germany.
Oncogene. 1999 Aug 19;18(33):4663-71. doi: 10.1038/sj.onc.1202842.
Some chromosomal translocations involved in the origin of leukemias and lymphomas are due to malfunctions of the recombinatorial machinery of immunoglobulin and T-cell receptor-genes. This mechanism has also been proposed for translocations t(4;11)(q21;q23), which are regularly associated with acute pro-B cell leukemias in early childhood. Here, reciprocal chromosomal breakpoints in primary biopsy material of fourteen t(4;11)-leukemia patients were analysed. In all cases, duplications, deletions and inversions of less than a few hundred nucleotides indicative of malfunctioning DNA repair mechanisms were observed. We concluded that these translocation events were initiated by several DNA strand breaks on both participating chromosomes and subsequent DNA repair by 'error-prone-repair' mechanisms, but not by the action of recombinases of the immune system.
一些与白血病和淋巴瘤起源相关的染色体易位是由于免疫球蛋白和T细胞受体基因重组机制的故障所致。这种机制也被认为与t(4;11)(q21;q23)易位有关,后者常与幼儿期的急性前B细胞白血病相关。在此,对14例t(4;11)白血病患者原发活检材料中的相互染色体断点进行了分析。在所有病例中,均观察到小于几百个核苷酸的重复、缺失和倒位,这表明DNA修复机制存在故障。我们得出结论,这些易位事件是由两条参与染色体上的多个DNA链断裂引发的,随后通过“易错修复”机制进行DNA修复,而非由免疫系统的重组酶作用引发。