Identification of the HTLV-1 carriers with high risk for adult T-cell leukemia

人类嗜t淋巴病毒1型（HTLV-1）是成人t细胞白血病（ATL）的病原体。然而，只有5%的HTLV-1运营商最终开发了ATL。因此，ATL的风险因病例而异。本研究的目的是建立识别高风险携带者的方法/诊断工具。首先，我们分析了54例HTLV-1携带者，他们的外周血样本至少采集两次，间隔10年。采用实时荧光定量PCR法测定原病毒DNA载量。在24例前病毒载量小于1%的病例中（外周血单个核细胞或PBMC中的感染细胞），其水平在0.28%至0.26%之间无显著变化。而在原病毒载量大于等于1%的30例中，原病毒载量从0.28%显著下降到0.26% （p<0.005）。迄今为止，人们认为HTLV 1载体的原病毒载量在很长一段时间内不会发生变化。当原病毒载量较高时，本研究的发现并不支持这一概念。这一结果可能提示，并非所有病毒载量较高的HTLV-1携带者都有发生ATL的高风险。然而，原病毒载量在几个原病毒载量高的携带者中发现增加。目前正在进行HTLV-1感染细胞的克隆分析和t细胞受体γ (TCRγ)基因的重排。此外，Sasaki等人报道了一种新的恶性肿瘤相关基因产物TSLC-1在ATL细胞中表达。HTLV-1携带者的TSLC-1现在也在随访超过10年的人群中进行测量。我们期望这些新标记的组合将使我们能够识别具有ATL发展高风险的HTLV-1携带者。

Human T-lymphotropic virus type 1 (HTLV-1) is a causative agent of adult T-cell leukemia (ATL). However, only five percents of HTLV-1 carriers develop ATL eventually. Therefore, the risk for ATL varied from case to case. The aim of this study is to establish the methods/diagnostic tools for identifying high risk carriers. First we have analyzed 54 HTLV-1 carriers whose peripheral blood samples were obtained at least twice with 10 years interval. The proviral DNA loads were measured by real-time PCR. In 24 cases whose proviral loads were less than 1% (infected cells among peripheral blood mononuclear cells or PBMC), the levels did not change significantly from 0.28% to 0.26%. However, in 30 cases whose proviral loads were more than or equal to 1%, the levels decreased significantly from 0.28% to 0.26% (p<0.005). Thus far, it was considered that the proviral loads in HTLV 1 carriers do not change for long time. The finding in the current study did not support this concept when the proviral loads were high. This result may indicate that not all of HTLV-1 carriers with high proviral loads are high risk for developing ATL. However, the proviral loads were found to increase in the several carriers with high proviral loads. The analysis of clonality of HTLV-1 infected cells and the rearrangement in the T-cell receptor-γ (TCRγ ) gene are now undergoing. In addition, a novel malignancy-associated gene product, TSLC-1, was reported to be expressed in ATL cells by Sasaki et al. TSLC-1 is also now measured in the HTLV-1 carriers who have been followed-up more than 10 years. We expect that the combination of these novel markers will enable us to identify the HTLV-1 carriers with high risk for ATL development.