Nucleic Acid Studies on the Pathogenesis of Leukaemia

S ummary . Recent work has lent strong support for the viral hypothesis of pathogenesis of human leukaemia. In laboratory animals both horizontal transmission from one individual to another by inoculation of leukaemia virus in the newborn, and vertical transmission through subsequent generation, have been shown to occur. With some animal leukaemias, and in general in human leukaemia, virus‐like particles cannot be detected by the electron microscope. It is generally accepted, however, that oncogenic virus infection can be transmitted through viral nucleic acids alone. Although oncogenic DNA viruses such as the Ebstein‐Barr virus might be the agent of Burkitt's lymphoma, tumour viruses which cause leukaemia in animals are usually RNA, and RNA viruses are the more likely candidates as viral agents for human leukaemia. RNA molecules with nucleotide sequences related to those of animal RNA tumour viruses have been found in human leukaemia, lymphoma, sarcoma and carcinoma cells. Such RNA molecules have the size of 70S RNA and are contained in a complex with reverse transcriptase. Nucleotide sequences, related to sequences of known RNA tumour viruses, have also been detected in human leukaemic cell DNA. Viral DNA sequences appear to be integrated into the genome mainly in the DNA fraction having an intermediate repetition frequency. They are not enriched in the satellite DNAs, which are the most highly repeated sequence of the cellular genome. Normal cell genomes may contain endogenous viral sequences which are inactive and might have been transmitted vertically through many generations. Recent work indicates that inherited endogenous tumour virus nucleotide sequences are related in evolutionary related species. Therefore, it appears likely that a possible human leukaemia virus might be related to primate leukaemia viruses.