A novel and cytogenetically cryptic t(7;21)(p22;q22) in acute myeloid leukemia results in fusion of RUNX1 with the ubiquitin-specific protease gene USP42
A novel and cytogenetically cryptic t(7;21)(p22;q22) in acute myeloid leukemia results in fusion of RUNX1 with the ubiquitin-specific protease gene USP42
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DOI：
10.1038/sj.leu.2404076
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发表时间：
2006-02-01
期刊：
影响因子：
11.4
通讯作者：
Panagopoulos, I
中科院分区：
文献类型：
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作者：
Paulsson, K;Békássy, AN;Panagopoulos, I
虽然许多血液系统恶性肿瘤的染色体异常是可识别的细胞遗传学，一些只能检测到使用分子方法。我们描述了一种新的隐匿性t（7;21）（p22;q22）在急性髓系白血病（AML）。FISH、3 'RACE和RT-PCR揭示了涉及RUNX 1和泛素特异性蛋白酶（USP）基因USP 42的融合。基因组断裂点位于RUNX 1的内含子7和USP 42的内含子1。在转录水平和基因组水平均未检测到相互嵌合体，FISH显示USP 42的50部分缺失。USP 42映射到以节段性重复为特征的7 p22区域。值得注意的是，17 kb的重复子存在于USP 42近端的1 Mb和RUNX 1近端的3 Mb处;这些可能在t（7; 21）的发生中很重要。这是恶性血液病中的第二个隐性RUNX 1易位，也是AML中的第一个隐性RUNX 1易位。以前没有报道过USP在白血病中重排。USP 42在细胞中的活性尚不清楚，但我们在这里表明它在正常骨髓、原发性AML和癌细胞系中表达。它参与t（7; 21）表明泛素相关通路的失调可能在AML中具有重要的病理意义。
Although many of the chromosomal abnormalities in hematologic malignancies are identifiable cytogenetically, some are only detectable using molecular methods. We describe a novel cryptic t(7;21)(p22;q22) in acute myeloid leukemia (AML). FISH, 3'RACE, and RT-PCR revealed a fusion involving RUNX1 and the ubiquitin-specific protease (USP) gene USP42. The genomic breakpoint was in intron 7 of RUNX1 and intron 1 of USP42. The reciprocal chimera was not detected - neither on the transcriptional nor on the genomic level - and FISH showed that the 50 part of USP42 was deleted. USP42 maps to a 7p22 region characterized by segmental duplications. Notably, 17 kb duplicons are present 1Mb proximal to USP42 and 3Mb proximal to RUNX1; these may be important in the genesis of t(7; 21). This is the second cryptic RUNX1 translocation in hematologic malignancies and the first in AML. The USPs have not previously been reported to be rearranged in leukemias. The cellular context in which USP42 is active is unknown, but we here show that it is expressed in normal bone marrow, in primary AMLs, and in cancer cell lines. Its involvement in the t(7; 21) suggests that deregulation of ubiquitin-associated pathways may be pathogenetically important in AML.