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

人类嗜T淋巴细胞病毒1型（HTLV-1）是成人T细胞白血病（ATL）的病原体。然而，只有五个HTLV-1载体的继承者最终开发了ATL。因此，ATL的风险因病例而异。本研究的目的是建立方法/诊断工具，以确定高风险的运营商。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了两次，间隔10年。通过实时PCR测量前病毒DNA载量。在24例前病毒载量小于1%（外周血单个核细胞或PBMC中的感染细胞）的病例中，水平从0.28%至0.26%没有显著变化。而前病毒载量≥ 1%的30例患者，其前病毒载量从0.28%降至0.26%（P<0.005）。迄今为止，人们认为HTLV 1携带者中的前病毒载量长时间不变。当前研究中的发现在前病毒负荷高时不支持这一概念。这一结果可能表明，并非所有高前病毒载量的HTLV-1携带者都是发展ATL的高风险。然而，前病毒载量增加，发现在几个载体与高前病毒载量。HTLV-1感染细胞的克隆性和T细胞受体γ（TCRγ）基因重排的分析正在进行中。此外，Sasaki等报道了一种新的恶性相关基因产物TSLC-1在ATL细胞中表达。TSLC-1现在也在随访超过10年的HTLV-1携带者中进行了测量。我们希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.