Mml1, a new common integration site in murine leukemia virus-induced promonocytic leukemias maps to mouse chromosome 10

MuLV-induced myeloid leukemias (MML) having promonocytic characteristics are produced with high incidence in some strains of adult mice that are undergoing chronic peritoneal inflammation. Previously we showed that many leukemias have rearrangements of the c-myb locus due to insertional mutagenesis, however, we also identified a number of leukemias that had proviral integrations in the absence of c-myb rearrangement. In the present study, a new locus, Mm/1, was found to be a target of insertional mutagenesis in 10 of the promonocytic leukemias that lacked c-myb alterations. Chromosomal mapping studies, performed using progeny from interspecies backcross mice generated by mating (BALB/cAn X M. spretus)F-1 females to BALB/cAN males, determined that Mm/1 is located on the proximal end of mouse chromosome 10. Interestingly, there were no recombinants between c-myb and Mm/1 in 101 backcross progeny and Mm/1 was mapped approximately 20-25 kb upsteam of c-myb. Interestingly, c-myb mRNA and Myb protein are expressed at levels similar to the levels observed in myeloid progenitor cells, but are not overexpressed. It is anticipated that future experiments will determine whether Mm/1 integration prevents down regulation of c-myb expression or activates another gene on chromosome 10. (C) 1996 Academic Press, Inc.