Franchini G, Wong-Staal F, Gallo R C
J Invest Dermatol. 1984 Jul;83(1 Suppl):63s-66s. doi: 10.1111/1523-1747.ep12281191.
We describe previously published work as well as new data on the molecular biology of human T-cell leukemia virus (HTLV) and its associated disease, adult T-cell leukemia-lymphoma (ATLL). This specific kind of disease is endemic to certain areas of Japan and the Caribbean, and several isolated cases have been described also in the United States, Israel, South America, and Africa. The disease is probably also endemic to Africa and South America, but sufficient studies of these areas have not been performed. We have molecularly cloned the HTLV genome and used the viral DNA as a probe in a large molecular study of the DNAs of human hematopoietic malignancies. The results showed that HTLV sequences could be detected in the fresh leukemic cells of all cases of ATLL tested. The neoplastic cells are of clonal origin and contain one or few copies of integrated HTLV. Detailed comparative analyses by restriction enzyme mapping of the proviral DNA in U.S., Japanese, Caribbean, and Israeli cases revealed that the viruses are almost indistinguishable. The DNA from neoplastic cells of other cases of hematopoietic neoplasias analyzed were negative for HTLV sequences with the exception of two. DNA from cells of a patient (MO) with a T-cell variant of hairy cell leukemia did contain a provirus only distantly related to HTLV (less than 10% of DNA sequence homology). The virus isolated from the MO cells has been designated HTLV-II. The second case was a patient with chronic myeloid leukemia whose cells contained exogenous DNA sequences distantly related to HTLV. Different fragments of the clones HTLV genome have been used to hybridize to DNA from uninfected normal tissues of several vertebrate species, including humans, in a search for cell-derived sequences related to the HTLV genome. No homologous sequences were found except sequences distantly related to the pol and env genes, indicating that HTLV does not carry a cellularly derived onc gene. Surprisingly, however, infection of normal human fresh T cells by HTLV transforms them into cells with permanent growth and with several other properties similar to neoplastic T cells. We have also studied the expression of viral and cellular genes in fresh and cultured neoplastic cells from patients with ATLL. Several species of viral mRNAs are always detected in the cultured neoplastic cells, whereas in some fresh samples expression of normal mRNA was not detected.(ABSTRACT TRUNCATED AT 400 WORDS)
我们描述了先前已发表的研究成果以及关于人类T细胞白血病病毒（HTLV）及其相关疾病——成人T细胞白血病淋巴瘤（ATLL）的分子生物学新数据。这种特定疾病在日本和加勒比地区的某些区域呈地方流行态势，在美国、以色列、南美洲和非洲也有几例孤立病例的报道。该疾病在非洲和南美洲可能同样呈地方流行态势，但尚未对这些地区进行充分研究。我们已对HTLV基因组进行了分子克隆，并将病毒DNA用作探针，对人类造血系统恶性肿瘤的DNA进行了大规模分子研究。结果显示，在所检测的所有ATLL病例的新鲜白血病细胞中均可检测到HTLV序列。肿瘤细胞起源于克隆，并且含有整合的HTLV的一个或少数几个拷贝。通过对美国、日本、加勒比地区和以色列病例中的前病毒DNA进行限制性酶切图谱分析的详细比较研究发现，这些病毒几乎难以区分。除两例之外，所分析的其他造血系统肿瘤病例的肿瘤细胞DNA中HTLV序列均呈阴性。一名患有毛细胞白血病T细胞变异型的患者（MO）的细胞DNA确实含有一种与HTLV仅有远缘关系的前病毒（DNA序列同源性低于10%）。从MO细胞中分离出的病毒被命名为HTLV-II。第二例是一名慢性髓性白血病患者，其细胞含有与HTLV仅有远缘关系的外源DNA序列。已使用HTLV基因组克隆的不同片段与包括人类在内的几种脊椎动物物种未感染的正常组织的DNA进行杂交实验，以寻找与HTLV基因组相关的细胞衍生序列。除了与pol和env基因仅有远缘关系的序列外，未发现同源序列，这表明HTLV不携带细胞衍生的癌基因。然而，令人惊讶的是，HTLV感染正常人类新鲜T细胞会将其转化为具有永久生长能力且具备其他一些与肿瘤性T细胞相似特性的细胞。我们还研究了ATLL患者新鲜及培养的肿瘤细胞中病毒基因和细胞基因的表达情况。在培养的肿瘤细胞中总能检测到几种病毒mRNA，而在一些新鲜样本中未检测到正常mRNA的表达。（摘要截选至400词）
