Linkage on chromosome 10 of several murine retroviral integration loci associated with leukaemia

Abstract

Mml loci have been identified as provirus integration sites among a subset of monocytic tumours induced by murine leukaemia virus (MuLV) infection of BALB/c and DBA/2 mice. These myeloid leukaemias contain a retrovirus integrated on chromosome 10 in proximity to the c-myb locus; however, c-myb expression was not altered. Detailed physical mapping enabled placement of the retroviral integration sites ∼25 kb (Mml1), ∼51 kb (Mml2), and ∼70 kb (Mml3) upstream of the c-myb locus. Furthermore, the Fti1 (fit-1) locus, a common integration site in feline leukaemia virus-induced T cell lymphomas, was mapped upstream of Mml3. Sequence analysis of Mml1, Mml2 and Mml3 loci (39·6, 16·4 and 5·9 kb, respectively) in conjunction with the BLAST (basic local alignment search tool) homology searches against the expressed sequence tag (EST) database and the use of gene/exon prediction programs revealed potential coding sequences that were not confirmed by Northern analysis or RT–PCR. The sequences between c-myb and Fti1, which were shown to include two potential scaffold/matrix attachment regions (S/MARs), are most likely regulatory in nature. An extended search for transcribed sequences far upstream of Mml3 revealed five genes, four of which were expressed in multiple tissues in mice. These genes could not be linked to tumour formation by the virus but their homologous sequences were found on human chromosome 6, thus allowing extension of the syntenic region on mouse chromosome 10 to approximately 250 kb.