IN-VITRO ESTABLISHMENT OF AIDS-RELATED LYMPHOMA CELL-LINES - PHENOTYPIC CHARACTERIZATION, ONCOGENE AND TUMOR-SUPPRESSOR GENE LESIONS, AND HETEROGENEITY IN EPSTEIN-BARR-VIRUS INFECTION

Lymphoma represents a major source of morbidity and mortality among AI DS patients. AIDS-associated non-Hodgkin lymphomas (AIDS-NHL) are almo st invariably B-cell derived, are classified as high or intermediate g rade lymphomas, and display three main histologic types: namely, small non-cleaved cell lymphoma (SNCCL), large cell immunoblastic plasmacyt oid lymphoma (LC-IBPL), and large cell lymphoma (LCL). Here we report the in vitro establishment of three new AIDS-NHL cell lines (termed HB L-1, HBL-2, and HBL-3) derived from three AIDS-SNCCL patients differin g in primary tumor sites and risk factors for HIV infection. The deriv ation of the cell lines from the original tumor clones was established by immunophenotypic and molecular genetic analysis. These cell lines display clonal immunoglobulin gene rearrangement, express surface immu noglobulin and B-cell restricted markers, and exhibit a phenotype cons istent with SNCCL. Monoclonal Epstein-Barr virus infection was found i n only one of the cell lines (HBL-1). Cytogenetic analysis demonstrate d the presence of a chromosomal translocation involving the c-myc prot o-oncogene and an immunoglobulin locus in all three cell lines. The pa ttern of genetic lesions detected in HBL-1, HBL-2, and HBL-3 reflects that found in primary AIDS-SNCCL and includes activation of the c-myc oncogene as well as inactivation of the p53 tumor suppressor gene. The se cell lines should prove useful in studies of the biological, immuno logical, and viral factors involved in AIDS-associated lymphomagenesis .