Integration of human T-cell leukemia virus type 1 in genes of leukemia cells of patients with adult T-cell leukemia
Integration of human T-cell leukemia virus type 1 in genes of leukemia cells of patients with adult T-cell leukemia
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DOI：
10.1111/j.1349-7006.2004.tb03207.x
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发表时间：
2004-04-01
期刊：
影响因子：
5.7
通讯作者：
Miwa, M
中科院分区：
文献类型：
--
作者：
Hanai, S;Nitta, T;Miwa, M
成人t细胞白血病（ATL）发生在人t细胞白血病病毒1型（HTLV-1）长期持续感染后。然而，HTLV-1致瘤的机制尚不清楚。据报道，ATL的发病率曲线随年龄的变化符合多阶段癌变模型。虽然HTLV-1是一种致癌逆转录病毒，但由于染色体上的确切整合位点尚未分析，因此目前尚未考虑ATL中插入突变作为多阶段癌变过程中的一个步骤的致癌机制。在这里，我们利用最近可用的人类基因组数据库确定了HTLV-1在人类染色体上的精确整合位点。我们从23例ATL中分离出25个HTLV-1整合位点。有趣的是，13个（52%）整合位点在基因内，这一比例显著高于随机整合情况下的预期（P=0.043, chi(2)检验）。这些结果表明，HTLV-1在首次感染时优先整合基因是其特征之一。但考虑到其中一些基因与细胞生长调控有关，HTLV-1与生长相关基因或近生长相关基因的整合可能有助于ATL多阶段癌变过程中HTLV-1感染细胞的克隆选择。
Adult T-cell leukemia (ATL) occurs after a long latent period of persistent infection by human T-cell leukemia virus type 1 (HTLV-1). However, the mechanism of oncogenesis by HTLV-1 remains to be clarified. It was reported that the incidence curve of ATL versus age was consistent with a multistage carcinogenesis model. Although HTLV-1 is an oncogenic retrovirus, a mechanism of carcinogenesis in ATL by insertional mutagenesis as one step during multistage carcinogenesis has not been considered thus far, because the exact integration sites on the chromosome have not been analyzed. Here we determined the precise HTLV-1 integration sites on the human chromosome, by taking advantage of the recently available human genome database. We isolated 25 integration sites of HTLV-1 from 23 cases of ATL. Interestingly, 13 (52%) of the integration sites were within genes, a rate significantly higher than that expected in the case of random integration (P=0.043, chi(2) test). These results suggest that preferential integration into genes at the first infection is a characteristic of HTLV-1. However considering that some of the genes are related to the regulation of cell growth, the integration of HTLV-1 into or near growth-related genes might contribute to the clonal selection of HTLV-1-infected cells during multistage carcinogenesis of ATL.