GRAFFI MURINE LEUKEMIA-VIRUS - MOLECULAR-CLONING AND CHARACTERIZATIONOF THE MYELOID LEUKEMIA-INDUCING AGENT

The Graffi murine leukemia virus (MuLV) is a retroviral mixture that i nduces predominantly myeloid leukemia in several inbred strains of mic e. To analyze the viral component responsible for the myeloid leukemog enesis, we cloned several proviruses from a Graffi MuLV-infected cell line. Several infectious molecular clones were obtained that could be classified into two distinct groups of infectious MuLV. Both types of MuLV were nondefective, ecotropic, and NB tropic and induced granulocy tic leukemia in BALB/c and NFS mice. Restriction enzyme analysis and m olecular hybridization with several MuLV probes on one molecular clone from each group revealed that both groups are closely related to each other but are clearly distinct from all known retroviruses. One compo nent of MuLV, however, induced leukemia with a shorter latency period and harbored a lengthier long terminal repeat. The long terminal repea t of the more leukemogenic component of MuLV had acquired a 60-bp perf ect duplication in the U3 region. Analysis of the tumor DNAs with prob es for the mouse T-cell receptor and immunoglobulin heavy chain genes revealed frequent rearrangements with one or both probes. This concomi tant expression by leukemic cells of markers of different lineages, ob served in human leukemias, has been termed ''lineage infidelity'' and confirms that the latter rearrangements are not restricted to hematopo ietic precursors committed to lymphoid differentiation.