Biology and virology of the human malignant lymphomas: 1st Milford D. Schulz Lecture

Abstract

Permanent cell lines have been established from twelve diffuse histiocytic lymphomas (SU-DHL-1 to -12), three American Burkitt's lymphomas (SU-AmB-1 to -3), two acute lymphoblastic leukemias (SU-ALL-1 and -2), and three diffuse undifferentiated lymphomas (SU-DUL-1, -2, and -3). The cultured cells displayed neoplastic characteristics, as manifested by heterotransplantability in congenitally athymic nude mice and by the presence of cytogenetic abnormalities in early passage generations. Functional and marker studies revealed that the three American Burkitt's lymphomas, as well as several of the diffuse histiocytic and undifferentiated lymphomas, were of B-lymphocytic origin, whereas the two acute lymphoblastic leukemias were both of T-lymphocytic origin. Two of the cell lines, SU-DHL-1 and -2, appeared to be of true histiocytic origin; two others exhibited no markers and were designated as "null" cells. All ten of the DHL cell lines studied to date, as well as SU-DUL-1, have been devoid of Epstein-Barr virus (EBV) genomes by the EBNA test, whereas two of the three American Burkitt's lymphoma cell lines were positive. Spontaneous production of a C-type RNA virus was first detected in post-mitochondrial cytoplasmic fractions and culture fluids of the SU-DHL-1 cell line. Screening assays for the detection of reverse transcriptase-positive particles in the culture fluids of the other cell lines indicate that eight of the fifteen cell lines tested to date have spontaneously initiated C-type RNA virus production. After partial purification by ion-exchange and affinity chromatography, the reverse transcriptases of the virus isolated from SU-DHL-1 cells is partially inhibited by antibodies to the reverse transcriptases of C-type viruses of subhuman primate and endogenous feline, but not of murine, origin. Conversely, antibody prepared against the purified SU-DHL-1 viral reverse transcriptase, at concentrations which maximally inhibit the homologous enzyme, partially inhibits the reverse transcriptases of subhuman primate C-type viruses, but has little or no inhibitory activity against the reverse transcriptases of feline or murine leukemia viruses. The viruses produced by the SU-DHL-1 and SU-AmB-3 cell lines have been shown to be infectious for normal human peripheral blood mononuclear cells, normal human bone marrow cells, and certain human lymphoblastoid cell lines. After infection by these viruses, normal human peripheral blood mononuclear cells and human bone marrow cells have exhibited striking changes in growth behavior and morphology which, though not permanently sustained, have many of the features of abortive transformation.