Division of Molecular Therapy, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
PLoS One. 2013;8(1):e53728. doi: 10.1371/journal.pone.0053728. Epub 2013 Jan 22.
In a recent study to purify adult T-cell leukemia-lymphoma (ATL) cells from acute-type patients by flow cytometry, three subpopulations were observed in a CD3 versus CD7 plot (H: CD3(high)CD7(high); D: CD3(dim)CD7(dim); L: CD3(dim)CD7(low)). The majority of leukemia cells were enriched in the L subpopulation and the same clone was included in the D and L subpopulations, suggesting clonal evolution. In this study, we analyzed patients with indolent-type ATL and human T-cell leukemia virus type I (HTLV-I) asymptomatic carriers (ACs) to see whether the CD3 versus CD7 profile reflected progression in the properties of HTLV-I-infected cells.
Using peripheral blood mononuclear cells from patient samples, we performed multi-color flow cytometry. Cells that underwent fluorescence-activated cell sorting were subjected to molecular analyses, including inverse long PCR.
In the D(%) versus L(%) plot, patient data could largely be categorized into three groups (Group 1: AC; Group 2: smoldering- and chronic-type ATL; and Group 3: acute-type ATL). Some exceptions, however, were noted (e.g., ACs in Group 2). In the follow-up of some patients, clinical disease progression correlated well with the CD3 versus CD7 profile. In clonality analysis, we clearly detected a major clone in the D and L subpopulations in ATL cases and, intriguingly, in some ACs in Group 2.
We propose that the CD3 versus CD7 plot reflects progression of disease stage in patients infected with HTLV-I. The CD3 versus CD7 profile will be a new indicator, along with high proviral load, for HTLV-I ACs in forecasting disease progression.
在最近一项通过流式细胞术从急性型患者中纯化成人 T 细胞白血病-淋巴瘤（ATL）细胞的研究中，在 CD3 与 CD7 的散点图中观察到三个亚群（H：CD3（高）CD7（高）；D：CD3（低）CD7（低）；L：CD3（低）CD7（低））。大多数白血病细胞富集在 L 亚群中，同一克隆包含在 D 和 L 亚群中，提示克隆进化。在这项研究中，我们分析了惰性型 ATL 患者和人类 T 细胞白血病病毒 I 型（HTLV-I）无症状携带者（AC），以观察 CD3 与 CD7 图谱是否反映了 HTLV-I 感染细胞特性的进展。
使用来自患者样本的外周血单核细胞，我们进行了多色流式细胞术。对经荧光激活细胞分选的细胞进行分子分析，包括反转录长 PCR。
在 D（%）与 L（%）的散点图中，患者数据可大致分为三组（组 1：AC；组 2：惰性和慢性型 ATL；组 3：急性型 ATL）。然而，也有一些例外（例如，组 2 中的 AC）。在一些患者的随访中，临床疾病进展与 CD3 与 CD7 图谱密切相关。在克隆性分析中，我们在 ATL 病例中清楚地检测到 D 和 L 亚群中的主要克隆，而且在组 2 中的一些 AC 中也存在，这令人好奇。
我们提出 CD3 与 CD7 图谱反映了 HTLV-I 感染患者疾病阶段的进展。CD3 与 CD7 图谱将成为一个新的指标，与高前病毒载量一起，用于预测 HTLV-I AC 疾病进展。
