IN-VITRO INFECTION OF LEUKEMIC BONE-MARROW WITH HTLV-I GENERATES IMMORTALIZED CELL-LINES EXPRESSING T OR MYELOID CELL PHENOTYPE

Leukemic bone marrow cells (>90% blasts) of a patient with acute myelo blastic leukemia (AML), non-treated or pretreated in vitro with a muta genic triazene compound, were infected with HTLV-I by coculture with i rradiated virus-donor cells. Immortalized, HTLV-I+, double-positive CD 4/CD8 euploid T cell lines, expressing HLA class I/II monomorphic dete rminants, and inappropriate myeloid and progenitor cell markers (ie CD 13, CD14, CD15 and CD33 antigens) were obtained. In one out of 10 tria zene-pretreated samples, HTLV-I infection resulted in the appearance o f a rapidly growing triploid cell line tie MTLC1 line) showing: (1) my eloid but not lymphoid phenotype; (2) beta and delta T cell receptor i n germline configuration; (3) integrated, complete and incomplete HTLV -I provirus genome (also detected in a number of MTLC1 clones); (4) a high percentage of cells positive for non-specific cross-reacting anti gen (a CEA-related molecule present on myeloid cells) under the influe nce of gamma-interferon; (5) absence of HLA class I/II antigen express ion; (6) absence of tax gene transcription. Blast cell proliferation w as marginal or absent when leukemic marrow was not subjected to retrov iral infection. These results show that exposure of leukemic bone marr ow to HTLV-I can be followed by immortalization of T and myeloid cells . Although no data are available to establish whether tax expression p layed a role in the early phase of the immortalization process of MTLC 1 line, fax gene product was not required for maintaining longterm gro wth of MTLC1 cells.