Important note: Information in this article was accurate in 1985. The state of the art may have changed since the publication date.
MOLECULAR BIOLOGY OF HTLV
Genetic and Phenotypic Markers of Tumors. Aaronson SA, Frati L, Verna R, eds. New York, Plenum Press, p. 337-44, 1984.. Unique Identifier : AIDSLINE ICDB/85615482 Wong-Staal F; Franchini G; Hahn B; Arya S; Gelmann EP; Manzari V; Gallo RC; Lab. of Tumor Cell Biology, NCI, NIH, Bethesda, MD 20205
Abstract:
Human T-cell leukemia/lymphoma virus (HTLV) is a family of related, human T-cell tropic retroviruses, consisting of at least two distinct subgroups, HTLV-I and HTLV-II. Molecular biological studies on HTLV are presented, focusing on a molecular epidemiological survey of human leukemias using cloned HTLV probes and on the molecular mechanism of transformation by HTLV in vivo and in vitro. Seroepidemiological studies have defined geographical areas where HTLV is endemic or present sporadically, as well as an association of HTLV with a subtype of mature T-cell malignancy now collectively called adult T-cells leukemia-lymphoma (ATLL). The cloned genomes of HTLV-I and HTLV-II were used to survey fresh peripheral blood leukocytes and tissues of patients (pts) with various hematologic malignancies. All of the typical (ATLL) samples, as well as a few cases of more benign cutaneous T-cell lymphoma, were positive for HTLV and contained closely related, if not identical, proviruses of HTLV-I subgroup. All ATLL leukemic cells, as well as established T-cell lines from HTLV-positive individuals, were mono- or oligo-clonally derived, as analyzed by provirus integration. To determine whether fresh and cultured cells represent similar infected cell populations, DNA from fresh peripheral blood cells of a pt was compared with the pt's cultured T cells. The results suggested that the clonally expanded leukemic cells lose their proliferative advantage so that the normal T cells infected in vivo during culture grow out and the cells initially go through a polyclonal phase; however, a specific cell population eventually dominates in culture. The possibility of onc gene activation after HTLV infection also was examined. Using cloned probes of sis, myc, myb, fes, abl, src, H-ras, and K-ras, no consistent activation was found of any onc gene in either in vitro infected cells or fresh leukemic cells, thus negating a requisite role of the onc gene tested in either initiation or maintenance of transformation. HTLV therefore falls into the class of chronic leukemia viruses; however, it is the only known chronic leukemia virus that can efficiently immortalize fresh human cells in vitro. (11 Refs)
Keywords: Cell Line DNA, Neoplasm/*ANALYSIS DNA, Viral/*ANALYSIS Human HTLV-BLV Viruses/*GENETICS Interleukin-2/GENETICS Leukemia/GENETICS/*MICROBIOLOGY Oncogenes Retroviridae Infections/GENETICS/*MICROBIOLOGY T-Lymphocytes/MICROBIOLOGY Transcription, Genetic MEETING PAPER
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