Molecular studies of human T-cell leukemia virus and adult T-cell leukemia.

Abstract

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)