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

人类T淋巴细胞白血病病毒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携带者最终发展为ATL。因此，急性淋巴细胞性白血病的风险因病例而异。这项研究的目的是建立识别高危携带者的方法/诊断工具。首先，我们分析了54名HTLV-1携带者，他们每隔10年至少采集两次外周血样本。用实时荧光定量聚合酶链式反应检测前病毒DNA载量。24例前病毒载量<1%的患者(外周血单个核细胞或PBMC中的感染细胞)，其水平在0.28%~0.26%之间无显著变化。但在30例前病毒负荷大于或等于1%的患者中，其水平从0.28%降至0.26%(p&lt；0.005)。到目前为止，人们认为HTLV-1携带者的前病毒负荷在很长一段时间内不会改变。当前病毒负荷较高时，当前研究中的发现不支持这一概念。这一结果可能表明，并非所有前病毒载量高的HTLV-1携带者都是发生ATL的高危人群。然而，在前病毒负荷高的几个携带者中，前病毒负荷被发现增加。HTLV1感染细胞的克隆性分析和T细胞受体γ(TcRγ)基因重排正在进行中。此外，Sasaki等人还报道了一种新的肿瘤相关基因产物TSLC-1在ATL细胞中表达。TSLC-1现在也在HTLV-1携带者中进行测量，这些携带者已经被跟踪了10年以上。我们期望这些新标记物的结合将使我们能够识别具有ATL高危发病风险的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.