Atlas M, Head D, Behm F, Schmidt E, Zeleznik-Le N H, Roe B A, Burian D, Domer P H
Department of Pediatrics, Northwestern University, Chicago, IL, USA.
Leukemia. 1998 Dec;12(12):1895-902. doi: 10.1038/sj.leu.2401223.
The t(9;11)(p22;q23) is the most common chromosomal translocation in topoisomerase II inhibitor therapy-related acute myeloid leukemia (tAML). This translocation fuses the MLL and AF9 proto-oncogenes producing a novel chimeric protein. In order to gain insight into the mechanism generating the t(9;11) and to clarify the role topoisomerase II inhibition may play in that mechanism we have cloned and sequenced the breakpoints from four tAML patients with the t(9;11). This sequence analysis identifies topoisomerase II consensus binding sequences near or at the chromosome 11 and chromosome 9 breakpoints in all four patients. One patient also had the consensus binding sequence for the TRANSLIN DNA-binding protein at the 9p22 and 11q23 breakpoints. Our results further support a direct role for topoisomerase II in the genesis of these tAML translocations.
t(9;11)(p22;q23)是拓扑异构酶II抑制剂治疗相关急性髓系白血病（tAML）中最常见的染色体易位。这种易位使MLL和AF9原癌基因融合，产生一种新的嵌合蛋白。为了深入了解产生t(9;11)的机制，并阐明拓扑异构酶II抑制在该机制中可能发挥的作用，我们对4例患有t(9;11)的tAML患者的断点进行了克隆和测序。该序列分析在所有4例患者的11号染色体和9号染色体断点附近或断点处鉴定出拓扑异构酶II共有结合序列。1例患者在9p22和11q23断点处还具有TRANSLIN DNA结合蛋白的共有结合序列。我们的结果进一步支持拓扑异构酶II在这些tAML易位发生过程中起直接作用。
