Nonspecific integration of the HTLV provirus genome into adult T-cell leukaemia cells

Abstract

Human T-cell leukaemia virus (HTLV), previously also reported as ATLV, is a recently identified retrovirus which is closely associated with adult T-cell leukaemia (ATL) endemic in southwestern Japan and the Caribbean. Determination of the total nucleotide sequence of the HTLV genome has revealed no typical onc gene acquired from the cellular sequence. Screening of the HTLV provirus genome in tumour cells has shown that in all cases of ATL examined, the primary tumour cells contained the provirus genome and were monoclonal with respect to the integration site of the provirus. These findings suggest that ATL leukaemogenesis may be due to insertional mutagenesis in which the provirus genome is integrated into a specific locus on the chromosomal DNA and then activates an adjacent cellular onc gene, a mechanism already demonstrated in avian lymphoma and erythroblastosis induced by avian leukosis viruses. A common site of HTLV provirus integration in leukaemic cells among some ATL patients was reported by Hahn et al. but subsequently retracted. However, this retraction does not imply the random integration of the proviruses. Independently, we have been testing this insertional mutagenesis model in ATL and report here that the provirus did not have a common locus of integration in 35 ATL patients and did not integrate on the same chromosome in 2 ATL patients.